PGxCheck...What is our DNA saying?




We need to consider how genetic information

can help us with respect to healthcare. We are able to perform genetic testing more readily,

but how are we using the results? Join in the discussion!


Personalized medicine and pharmacogenomics (the influence of genetics on drugs) is here. It is in its infancy and we all will watch it grow. From healthcare professionals to the general public, pharmacogenomics and the broader area of personalized medicine will present a learning curve.

This blog is made possible through an individual making their genetic information available. 

As we learn what this individual's genetics are telling us...and what it is not telling us, we will discuss it. I am sure there will be many questions. We will have individuals from pharmacy, genetics, ethics, law, and other disciplines adding their expertise and thoughts to the discussion. I sincerely hope you will contemplate the information, formulate your thoughts, and participate in the discussion!

The Personalized Medicine Pie and related items

There are many "sectors that must come together to make personalized medicine a standard. We talked about these briefly before. Look at the image below:

PM Pie
The image is from the Personalized Medicine Coalition the leading education and advocacy group regarding PM. You can find the document describing the 'pie' here. Recognize that as all of the pieces come together, we will be able to optimize personal healthcare. We will be able to get the right drug for the patient at the start, choosing a drug that is effective while avoiding adverse drug reactions, which will encourage patients to adhere to their drug therapy regimens. (i.e., they will not avoid taking their medication due to adverse effects). Including the patient's observations of their disease and treatment and related lifestyle, diet, and family history information (participatory medicine) is very important. That is a big piece of the pie...really important!

Again, the technology of DNA sequencing has allowed this to happen. We will not be able to afford to do studies to look at outcomes relative to all the different potential drug-gene interactions. We need to be able to do the best we can to provide the best therapies possible. From the pharmacy standpoint, genetics determines, in large part, the function of receptors, drug transporters and drug metabolizing enzymes.

While our understanding of drug-gene relationships is evolving, the use of genetics in drug therapy is being applied across therapeutic areas, with oncology and psychiatry leading the way. Here, in oncology tumor genetics can be used to guide some drug therapies, however, the genetics of all tumors have not been determined and likely will not be due to the 'chaos' that is cancer.

At any rate, one of the KEY changes occurring right now is the conversion to electronic records (EHR). This is being pushed by the government through the HITECH act which states that EHR must be used in a meaningful way after 2015. I have seen this change with my personal physicians office, where EHR implementation actually delayed genetic testing for clopidogrel use! Clearly there is a lot going on related to this field!

As we move forward, healthcare professions students, healthcare professionals, and the public at large will need to embrace PM medicine as it will help us move towards better health in an economically responsible way.


I had a question about the recent news (November 22, 2013), that 23andMe received a warning letter to stop selling their testing kits. The questions was essentially, "What's the problem with the test?" Here are my brief comments.

The problem is not so much with the test as it is with how the results are being used (statistical issues) . When earlier this year 23andMe decided to put forth stronger statements relating genetics and disease risk, they apparently 'crossed the line'. Not to mention the fact they had not communicated, apparently for six months with the FDA.


The lab testing is done on a very legitimate platform and is actually performed by LabCorps CLIA certified lab, so not much of an issue here. The big concern from the FDA's view, at least stated this way is the potential for false positive or false negative results, which are not different from any other potential from the same lab. It is just the information is put squarely in the consumers hands, without professional intervention. This is why it is so important to note for people that when we look at the genetics, we are looking at drug response only. This is still the most legitimate broad use of genotyping information. i.e., related to drug response. Although the letter does describe drug response results as an issue. This is why you are in this course and will become experts to understand,  interpret, and apply the information appropriately. Upon completion of the curriculum, you will be well-versed in this area!

Remember, one of the early points discussed in the blog was centered around the disease risk being 'relative' and NOT 'absolute'. For some consumers, this point is lost and has the potential to result in unintended consequences. Check out the FDA's letter to 23andMe by clicking here: letter.

Education and Personalized Medicine - A challenge to you!

We have been spending quite a bit of time on information related to disease risk and drug response and a bit of time on ethical issues and most recently, all the "pieces of the pie" that must come together to make personalized medicine a reality. Hopefully, society will come to accept personalized medicine and the use of DNA in a positive manner to improve health. Since our DNA DOES NOT CHANGE, we are "stuck" with our genetic influence on disease and drug response...this will NOT change with time.

What will change with time is the amount of information that is available and the opportunities to educate ourselves. The two therapeutic areas where most of the DNA information is currently being applied are oncology and psychiatry. Certainly in oncology, the DNA of some tumors are used to identify targeted drug therapy. Unfortunately, the cancer area is very difficult and each cancer appears to have its own genetics. So, while some cancers are better understood, the genetics of all cancer cells have eluded us. This is a very difficult area and we are learning more and more every day.

So, speaking of learning, here is the challenge. Please go online and search for any piece of information related to personalized medicine that you believe can be used to educate us about genetics, DNA, pharmacogenetics, or personalized medicine itself. Then post the link. I would like to see at least 50 posts!!! We will then have a repository of some information that can be useful.

The Breadth of Personalized Medicine - Personal Genome Evaluation

Personal genome evaluation (PGE) is a growing approach to understanding the influence of genetics on an individual's health. We have talked about a number of topics related to PGE, such as recently bringing up drug-gene interactions as a part of pharmacogenetics, but there is a broader context.

While drug-gene interactions are a component of pharmaco (drug) genetics, many other "pieces of the pie" make up the whole of personalized medicine. 

Consider the following as "pieces of the personalized medicine pie":

1. Medical education

2. Health care information technology

3. Regulation (policy)

4. Technology and tools

5. Insurance coverage and reimbursement

6. Genetic privacy and legal protections

Give us your thoughts on how these individual "pieces" help to make the "whole pie". Click on the title to check out this important document: 

Read about the given pieces mentioned above and comment as to why you feel one of more pieces are critical. Let's hear your thoughts!!!

What is a drug-gene interaction?

After the post on warfarin, I thought now would be a good time to talk about drug-gene interactions. With warfarin as an example, we can talk about a genetic-dynamic interaction and a genetic-kinetic interaction.

The interaction of a drug and a drug target (a target protein) produced by a variant gene (allele), such as a receptor (click here and click on "drug targets" to review the basics of what a receptor is) results in a genetic-dynamic interaction. In this case the "target protein" for warfarin is the enzyme vitamin K epoxide reductase (sub-unit 1); VKORC1. Warfarin inhibits the activation of vitamin K dependent clotting factors by interacting with VKORC1, resulting in decreased clotting. One of the common uses of warfarin is in patients with the irregular heart rhythm, called atrial fibrillation, where the risk clot formation and stroke is increased. Since this is a case of 'what the drug does to the body', i.e., warfarin inhibits clot formation, this is pharmacodynamics. When someone has a genetic variation resulting in decreased formation of VKORC1, such as the *2 variant, and warfarin is used, there is less target enzyme made and it takes less warfarin to inhibit clot formation. The interaction of warfarin with the product of a VARIANT gene is a drug-gene interaction.

The interaction of warfarin and a decreased or loss-of-function form of the (click here and read about drug metabolizing enzymes drug metabolizing enzyme)CYP2C9 produced by a variant gene (e.g. CYP2C9*2, CYP2C9*3), is a drug-gene interaction. Here, since this is the case of 'what the body does to the drug', i.e., CYP2C9 metabolizes warfarin, this is pharmacokinetic interaction.

So a drug has to interact with a product of a variant gene to be considered a drug-gene interaction. If there is a 'normal' gene producing a 'normal' protein drug target, no interaction would be observed.

Here are some gene forms, tell me if a drug interacts with a given gene (you choose), would there be an interaction?








Check out Look up the genes by clicking on the appropriate link under 'publication link'.

What if a person has one 'normal' gene from one parent and one variant gene from the other parent, would there be a drug-gene interaction? Let us know your thoughts!

If I had atrial fibrillation and needed warfarin...

Here is the description of atrial fibrillation from the National Heart Lung and Blood Institute (NHLBI):

Atrial fibrillation (A-tre-al fi-bri-LA-shun), or AF, is the most common type of arrhythmia (ah-RITH-me-ah). An arrhythmia is a problem with the rate or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, or with an irregular rhythm.

AF occurs if rapid, disorganized electrical signals cause the heart's two upper chambers—called the atria (AY-tree-uh)—to fibrillate. The term "fibrillate" means to contract very fast and irregularly.

In AF, blood pools in the atria. It isn't pumped completely into the heart's two lower chambers, called the ventricles (VEN-trih-kuls). As a result, the heart's upper and lower chambers don't work together as they should.

People who have AF may not feel symptoms. However, even when AF isn't noticed, it can increase the risk of stroke. In some people, AF can cause chest pain or heart failure, especially if the heart rhythm is very rapid.

AF may happen rarely or every now and then, or it may become an ongoing or long-term heart problem that lasts for years.

One of the goals of treating AF is to:

  • Prevent blood clots from forming, thus lowering the risk of stroke.

People who have AF are at increased risk for stroke. This is because blood can pool in the heart's upper chambers (the atria), causing a blood clot to form. If the clot breaks off and travels to the brain, it can cause a stroke.

Preventing blood clots from forming is probably the most important part of treating AF. The benefits of this type of treatment have been proven in multiple studies.

Doctors prescribe blood-thinning medicines to prevent blood clots. These medicines include warfarin (Coumadin®), dabigatran, heparin, and aspirin.

People taking warfarin (and some other) medicines need regular blood tests to check how well the medicines are working.

OK that is the information, adopted from the NHLBI. Now for some pharmacogenomic information. By the way, the strict definition of pharmacogenetics is the relationship between a single gene and drug response, whereas, pharmacogenomics is the relationship between all genes (the genome) and drug response...a slight difference. I use pharmacogenomics here, because there are, at least, two genes involved in an individual's response to warfarin. Here is my information:

23andMe 1

23andMe 2

So, how does this information impact the dosing of warfarin for me? Here is a dosing table for initial dosing of warfarin based on genetics. Please consider the following:


I know this is a "big chart" from the supplementary material provided by the Clinical Pharmacogenetic Implementation Consortium (CPIC), published in Clinical Pharmacology and Therapeutics in October of 2011 (free access article), however, you should be able to put together my genotype (*/*) and comment on my metabolizing of warfarin by the CYP2C9 metabolizing enzyme, based on my CYP2C9 genotype.

Then there is the issue of the drug (warfarin) target, here, an enzyme called VKORC1. Here is some information from the same CPIC source:

Individuals which have an A instead of a G at rs9923231 have increased sensitivity to warfarin. Here, there is less target protein made for warfarin to affect, so you need less warfarin...or in other words, there is warfarin sensitivity. So, look again at the above information and tell me what dose of warfarin you think I should start on, based solely on my genetics. I challenge you to look up warfarin and see what some of the adverse, or side effects there are and discuss what may happen to me if I get the wrong dose of warfarin. I look forward to some thoughts on this!

Metabolizer Phenotypes

In the previous post we discussed different 'metabolizer phenotypes' related to the specific drug metabolizing enzyme CYP2C19. Phenotype means how we 'express' our genetics. Some people express their genetics related to drug metabolism as 'poor metabolizers (PM)', meaning they have 'slow', decreased, or even absent metabolism, these individuals typically require lower doses of active drugs that are metabolized by the given enzyme. If the drug is a prodrug, and requires activation, a higher dose of the prodrug may be required, or another drug can be used. Some people are 'intermediate metabolizers (IM)', meaning that they have decreased metabolism relative to normal metabolism. These individuals typically require a lower dose of an active drug also, but not as low of a dose as a PM would require. Here, a prodrug may not work as well either as less drug would be activated. Some people are ultrarapid metabolizers (UM)', meaning they have increased metabolism relative to normal metabolism. These individuals typically require higher doses than a PM or IM and even a 'normal metabolizer'. These individuals can readily convert a prodrug to its active form. However, most individuals have a 'normal (extensive) metabolizer (EM)' phenotype. This has been called extensive metabolism, but that term can cause some confusion, so think of extensive as 'normal'.

As you will see, there are many different drug metabolizing enzymes. Some of these enzymes metabolize a relatively large percentage of drugs. The family of CYP (cytochrome P450) genes includes CYP2C19, as mentioned before, and CYP2D6, CYP2C9, and many others.

As you have seen, we utilize the star '*' nomenclature (e.g., *1/*2) to identify the two genes each person has (one from each parent) in what we call a genotype or diplotype (two genes). The '*' forms represent different genetics as introduced by a SNP (see post on September 04, 2013 at 7:56 AM EDT) or some other genetic variation. It is important to understand that the '*' nomenclature does not define phenotype the same way for each CYP. So, here is a challenge! The two links below are to current literature (Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines), which defines metabolism phenotype based on the '*' nomenclature. Below are some diplotypes for CYP2C19 and CYP2D6. In you post, define the phenotypes based on the diplotypes, here relating the genetics to metabolism. Note in your post, only provide two examples and leave the others for the next 'poster'. Thanks!

CYP2C19 Genotypes (example diplotypes; click HERE; read the table carefully):











CYP2D6 Genotypes (example diplotypes; click HERE; read the table carefully):
















So, 'have at it' and we will learn something about this '*' nomenclature!

Chest Pain, Coronary Artery Blockage and My Antiplatelet Therapy!

One of the aims of personalized medicine is to optimize drug therapy. This is a result of providing the patient with the right medication, which is going to work for them (efficacy), while avoiding adverse effects (adverse drug reactions). Avoiding adverse drug reactions will make the patient adhere to taking their medication. This is a "win-win-win" situation.

Here are my results relative to the drug metabolizing enzyme CYP2C19 and the drug clopidogrel (you may have seen commercials for the brand name Plavix) and these results would be very important if I were to requires an antiplatelet drug to keep my blood from forming dangerous clots that could result in a second heart attack and death...I will explain.

Let's say I suffer a heart attack and it is noted that one or more of the arteries that supply my heart tissue (muscle) are blocked with plaque. This can result in another clot and cause another heart attack, or death. It is somewhat common in this situation to have a stent (tube) placed in the arteries to keep blood flowing. This puts me at risk for a clot to form at the site of the stent and another heart attack. It is standard to give people with a stent at least two antiplatelet drugs. Typically aspirin and another drug. This can help prevent clot formation. One of the best selling drugs for this purpose is clopidogrel (Plavix). Clopidogrel is a prodrug, meaning it needs to be activated by the body to work. The gene that produces the metabolizing enzyme, a drug target protein, that 'activates' clopidogrel is CYP2C19. Notice the gene is italicized whereas earlier, the enzyme of the same name was NOT italicized. This is by convention and I thought I would just 'throw this information in'.

The issue is...that my genetics will dictate whether clopidogrel will work for me. Some people have a CYP2C19 gene that produces an inactive (loss-of-function) enzyme. Remember that we get a gene from each parent, so an individual can have two 'normal' genes, one 'normal' and one 'loss of function' gene or two 'loss-of-function' genes. There are other forms too, like a 'gain-of-function', but we will not discuss this further. We have a way of defining these potentials:

*1/*1 = normal/normal = normal (extensive) metabolizer
*1/*2 (and other *s, e.g., *3) = normal/loss-of-function = intermediate metabolizer
*2/*2 = loss-of-function/loss-of-function = poor metabolizer

Data shows that intermediate metabolizers and poor metabolizers should receive a drug other than clopidogrel.

So, the question is what am I? Well, here is the data:
CYP2C19 result_1


Notice a couple of things. First, the rs#. I think I mentioned this earlier, but if not... the rs# is a specific and unique identifier of a given SNP as found in the National Center for Biotechnology Information database called 'dbSNP'. So rs4244285 refers to the above SNP in the specific position on the CYP2C19 gene where A replaced G. G is the 'normal', most common base found at that position, so one parent passed along the A instead of a G. That single nucleotide change (polymorphism) resulted in me not being able to convert as much of the clopidogrel prodrug to its active form, meaning that I would be at increased risk of another clot, heart attack and death if I were using clopidogrel as a second antiplatelet medication. I have since confirmed my *1/*2 status by testing done in my lab.

From the personalized medicine standpoint, this testing allows for me to receive a drug that is efficacious (that will work for me; like prasugrel or ticagralor, i.e., something other than clopidogrel), will avoid an adverse event...hopefully, here avoiding a clot and death! Also, I will be adherent to the medication because it can be a matter of life or death!

So, time to look at some data and answer some questions. Click HERE to look at some data from the Clinical Pharmacogenetic Implementation Consortium (CPIC) and find the table that shows the frequency of the *2 form in various populations. Let's see which populations have the highest frequency of the loss-of-function *2 allele (gene form). Go ahead and put this in your comment. Also, think about what this may mean for a given individual from a specific population.



East Asian


Middle Eastern


South/Central Asia

This is helpful in considering who may be more likely to have a loss-of-function gene form (allele) when there is no individual genetic data. Who has what frequency? Who would you be most likely to give an antiplatelet drug, other than clopidogrel, to? Of course, we REALLY need the individuals genetic data! By the way, the reason we can do all this is that technology has advanced to allow us to look at DNA more efficiently! DNA testing is more available and affordable.

A preliminary look at drug response: Caffeine

Here is my first entry related to drug response. I am starting off with a result that is supported only by one study...not the strongest of data, but interesting nonetheless. I know that some of the terminology can be difficult, so I "cleaned the background information up a bit! I added a few [bracketed] comments. Note, use an online medical dictionary to look up some of the terms you may not be familiar with.

Coffee, CYP1A2 [CYP = cytochrome P450, a metabolizing enzyme] genotype, and risk of myocardial infarction.


Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.



The association between coffee intake and risk of myocardial infarction (MI) remains controversial. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers.


To determine whether CYP1A2 genotype modifies the association between coffee consumption and risk of acute nonfatal MI.


Cases (n = 2014) with a first acute nonfatal MI and population-based controls (n = 2014) living in Costa Rica between 1994 and 2004, matched for age, sex, and area of residence, were genotyped by restriction fragment-length polymorphism polymerase chain reaction. A food frequency questionnaire was used to assess the intake of caffeinated coffee.


Relative risk of nonfatal MI associated with coffee intake, calculated using unconditional logistic regression.


Intake of coffee was associated with an increased risk of nonfatal MI only among individuals with slow caffeine metabolism, suggesting that caffeine plays a role in this association.

Here is what 23andMe posted in  my results:

Caffeine Metabolism

Some people get jumpy after drinking a single cup of coffee, while others can gulp down a Venti Americano [what is this?] without feeling a thing. Part of that variability is due to the development of tolerance by regular coffee drinkers; but there are genetic differences in how people metabolize caffeine as well.

The following results are based on  Preliminary Research for 1 reported marker.

Caffeine and MI risk

Caffeine MI_2

I find this interesting, because if I drink a cup of coffee, which I don't regularly at all, let alone a Venti Americano, I get so 'jittery' I can't stand it. Also, I once took a dose of a drug called theophylline for a study and I could not come close to sleeping! See if you can find out how theophylline is related to caffeine!

At any rate, my genetics say I am a 'fast caffeine metabolizer'. Thank goodness!

Let's Talk Personalized Medicine, Pharmacogenetics, and Pharmacogenomics!

We have been looking at disease risk and what we would want to know or not know and some of the ethical issues related to genetic information. Perhaps, no greater advances have been achieved, to date, than the use of DNA information as applied to drug therapy. Across all therapeutic areas, oncology, cardiology, infectious diseases, neurology, etc., we are using DNA information in drug and drug dosage selection. Let's start of with some definitions and abbreviations and then we will move to individual drug-gene interactions and look at some real data.


First, a definition of 'Personalized Medicine' - 'Personalized Medicine' refers to the tailoring of medical treatment to the individual characteristics of each patient…to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment.  Preventative or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not.

Pharmacogenetics (PGt) - The study of a gene involved in response to a medication.

Pharmacogenomics (PGx) - The study of many genes, in some cases the entire genome (all our DNA) involved in response to a drug.

Recall from an earlier post - 'The human genome is made up of a sequence of four chemicals, called nucleotide bases and include adenine (A), guanine (G), thymine (T), and Cytosine(C). This sequence is our DNA and it is found in every cell of the body, that has a nucleus (i.e., nucleated cells), on 23 chromosomes. We get a set of chromosomes from each parent, so there are 46 chromosomes in each cell. The sequence of DNA from each parent is about three (3) billion bases long...the four chemicals in a long sequence. Based on DNA we are about 99.9% the same. Differences between individuals can be described as genetic variation. In some cases the genetic variation can be a result of a change in the sequence by one nucleotide base replacing another, such as an A replacing a G. For instance:


A sequence that is the most “common” sequence may be TCC CAG CTG GAA TCC GGT GTC


The variation may be: TCC CAG CAG GAA TCC GGT GTC, where A (adenine) replaced T (thymine).'

Take a couple of minutes and read again the information relating DNA variation to amino acid sequence alterations related to drug targets found at 'Drugs and Genes'. Click here: ( The 'DNA" pages and "Drug Targets' page will put us back into the right place to start talking about PGt!

Now we will start talking about genetic variation from individual to individual related to important 'targets' for drugs. Here, I call these targets pharmacogenetic or pharmacogenomic proteins, which include drug receptors, drug transporters, and drug metabolizing enzymes. We will discuss each of these.

Expanding GINA

Many States are using the Federal GINA as a baseline and expanding it to cover more for their individual state needs. Please read the short report form the "Genomics Law Report" found at


You can click HERE to access the document.

Genetic Discrimination - An example and the law

There have been a number of comments related to legal issues and genetic information, as well as one post referring to the Genetic Information Nondiscrimination Act (GINA). Consider the information from the U.S. Equal Employment Opportunities Commission (EEOC) explaining the 2008 legislation, found at and accessed September 23, 2013.

Genetic Information Discrimination

Title II of the Genetic Information Nondiscrimination Act of 2008 (GINA), which prohibits genetic information discrimination in employment, took effect on November 21, 2009.

Under Title II of GINA, it is illegal to discriminate against employees or applicants because of genetic information. Title II of GINA prohibits the use of genetic information in making employment decisions, restricts employers and other entities covered by Title II (employment agencies, labor organizations and joint labor-management training and apprenticeship programs - referred to as "covered entities") from requesting, requiring or purchasing genetic information, and strictly limits the disclosure of genetic information.

The EEOC enforces Title II of GINA (dealing with genetic discrimination in employment). The Departments of Labor, Health and Human Services and the Treasury have responsibility for issuing regulations for Title I of GINA, which addresses the use of genetic information in health insurance.

Definition of “Genetic Information”

Genetic information includes information about an individual’s genetic tests and the genetic tests of an individual’s family members, as well as information about the manifestation of a disease or disorder in an individual’s family members (i.e. family medical history). Family medical history is included in the definition of genetic information because it is often used to determine whether someone has an increased risk of getting a disease, disorder, or condition in the future. Genetic information also includes an individual's request for, or receipt of, genetic services, or the participation in clinical research that includes genetic services by the individual or a family member of the individual, and the genetic information of a fetus carried by an individual or by a pregnant woman who is a family member of the individual and the genetic information of any embryo legally held by the individual or family member using an assisted reproductive technology.

Discrimination Because of Genetic Information

The law forbids discrimination on the basis of genetic information when it comes to any aspect of employment, including hiring, firing, pay, job assignments, promotions, layoffs, training, fringe benefits, or any other term or condition of employment. An employer may never use genetic information to make an employment decision because genetic information is not relevant to an individual's current ability to work.

Harassment Because of Genetic Information

Under GINA, it is also illegal to harass a person because of his or her genetic information. Harassment can include, for example, making offensive or derogatory remarks about an applicant or employee’s genetic information, or about the genetic information of a relative of the applicant or employee. Although the law doesn't prohibit simple teasing, offhand comments, or isolated incidents that are not very serious, harassment is illegal when it is so severe or pervasive that it creates a hostile or offensive work environment or when it results in an adverse employment decision (such as the victim being fired or demoted). The harasser can be the victim's supervisor, a supervisor in another area of the workplace, a co-worker, or someone who is not an employee, such as a client or customer.


Under GINA, it is illegal to fire, demote, harass, or otherwise “retaliate” against an applicant or employee for filing a charge of discrimination, participating in a discrimination proceeding (such as a discrimination investigation or lawsuit), or otherwise opposing discrimination.

Rules Against Acquiring Genetic Information

It will usually be unlawful for a covered entity to get genetic information. There are six narrow exceptions to this prohibition:

  • Inadvertent acquisitions of genetic information do not violate GINA, such as in situations where a manager or supervisor overhears someone talking about a family member’s illness.
  • Genetic information (such as family medical history) may be obtained as part of health or genetic services, including wellness programs, offered by the employer on a voluntary basis, if certain specific requirements are met.
  • Family medical history may be acquired as part of the certification process for FMLA leave (or leave under similar state or local laws or pursuant to an employer policy), where an employee is asking for leave to care for a family member with a serious health condition.
  • Genetic information may be acquired through commercially and publicly available documents like newspapers, as long as the employer is not searching those sources with the intent of finding genetic information or accessing sources from which they are likely to acquire genetic information (such as websites and on-line discussion groups that focus on issues such as genetic testing of individuals and genetic discrimination).
  • Genetic information may be acquired through a genetic monitoring program that monitors the biological effects of toxic substances in the workplace where the monitoring is required by law or, under carefully defined conditions, where the program is voluntary.
  • Acquisition of genetic information of employees by employers who engage in DNA testing for law enforcement purposes as a forensic lab or for purposes of human remains identification is permitted, but the genetic information may only be used for analysis of DNA markers for quality control to detect sample contamination.

Confidentiality of Genetic Information

It is also unlawful for a covered entity to disclose genetic information about applicants, employees or members. Covered entities must keep genetic information confidential and in a separate medical file. (Genetic information may be kept in the same file as other medical information in compliance with the Americans with Disabilities Act.) There are limited exceptions to this non-disclosure rule, such as exceptions that provide for the disclosure of relevant genetic information to government officials investigating compliance with Title II of GINA and for disclosures made pursuant to a court order.

Relative to GINA, consider the following case of the Burlington Northern & Santa Fe Railway company (click here). Note that this case occurred prior to the GINA. Let's continue to share our thoughts! 

Would you want to know?

The implications of Alzheimer's disease (AD) are of concern, especially early onset. My anxiety has now 'peaked' as I scroll down to see my results. I was not anxious at all until I got to the actual point of looking at these results.


The APOE gene has been associated with risk of AD. There are three variants of the gene that infer different risk. These variants are determined by two single nucleotide changes (polymorphisms (SNPs)).


For me, the results indicate that for the first SNP of interest, my genotype is CC (remember one from each parent). The second SNP of interest indicates a genotype of TT.


Ok, what does this mean? First, the rs number is a specific and consistent number used to note that SNP. i.e., that single change at that point in the APOE gene. The combination of SNPs is used to determine the APOE variant. For me, the C + T (in both cases, I had two Cs and two Ts) = the variant E3, so with a C and T from mom and a C and T from dad, I am an E3/E3.


As it turns out, this variant inparts 'normal' risk. While I am a bit relieved that I was not E3/E4 or E4/E4, because E4 imparts increased risk of earlier onset AD, I know that more than 50% of people with AD do not have the E4 variant. The E4 variant, again, appears to impart increase risk of early onset AD. The E2 variant may be 'protective'.


In a study of over 3400 individuals, the frequency of the different APOE variants were:

E3/E3 - 63.9%

E3/E4 - 19%

E2/E3 - 13.7%

E4/E4 - 1.7%

E2/E4 - 1.3%

E2/E2 - 0.4%


Remember that your DNA does not change throughout your lifetime, so what you have DNA wise is what you have!

So I you want to know your risk of AD based on genetic markers (SNPs and gene variants)? If so, why? If not, why not? What are some of the ethical, legal, and social implications?

Disease Risk - Coronary Heart Disease (CHD)

Based on the information from 23andMe, I am in a group of individuals (those with similar genetics relative to markers for CHD) in which 32.8 out of 100 would develop coronary heart disease, where as an overall group of similar age and ethnicity would have 46.8 out of 100 develop CHD. So in this case, my odds of developing CHD are lower. Here the odds ratio relative to CHD is 0.7 (<1 is better than >1 and a value of ~1 would mean average risk). Check out the image below, taken from my results provided by 23andMe.


If this were YOUR results, what would be your thoughts? Think broadly here. We will look at your comments and I will add some thoughts.

A quick look at DNA, Amino Acids, and Proteins

Before we go on with more disease risk information, I wanted to point out a brief review that you need to go look at and read. This takes the previous post information about DNA just a bit "farther". For most of you, this will be a review, but I thought it best to have you look at a short notation on DNA, amino acids, and proteins. The following link is to a website set up for the general public by the Ohio Northern University Raabe College of Pharmacy and the University of Florida College of Pharmacy student chapters of the Personalized Medicine Coalition (PMC). The site is called "Drugs and Genes". For now, go to (click on) and click on the "DNA" tab next to "HOME" in the middle of the page. Read the information about DNA, amino acids, and proteins. We will refer to this site again in future posts. That''s it for this post!

Introductory Information and Disease Risk: Prostate Cancer!

I thought it best to have a baseline with the discussions starting with the disease risk information. 


The human genome is made up of a sequence of four chemicals, called nucleotide bases and include adenine (A), guanine (G), thymine (T), and Cytosine(C). This sequence is our DNA and it is found in every cell of the body, that has a nucleus (i.e., nucleated cells), on 23 chromosomes. We get a set of chromosomes from each parent, so there are 46 chromosomes in each cell. The sequence of DNA from each parent is about three (3) billion bases long...the four chemicals in a long sequence. Based on DNA we are about 99.9% the same. Differences between individuals can be described as genetic variation. In some cases the genetic variation can be a result of a change in the sequence by one nucleotide base replacing another, such as an A replacing a G. For instance:


A sequence that is the most “common” sequence may be TCC CAG CTG GAA TCC GGT GTC


The variation may be: TCC CAG CAG GAA TCC GGT GTC, where A (adenine) replaced T (thymine).


This is called a single nucleotide change or single nucleotide polymorphism (SNP, pronounced “snip”), since one chemical replaced another. This change may result in a difference from one individual to another. We will have some examples of this over the coming weeks.



Disease Risk: The information provides information about increased risk of disease, average risk of disease and decreased risk of disease. Let’s start with increased risk of disease. According to 23andMe, I have 1.5 x the average risk of getting prostate cancer.


How was this information provided to me? Through what is called the “odds calculator”, where 26.7 men with a genetic make-up like me, according to 23andMe will develop prostate cancer where as with average risk 17.8 men out of 100 will develop the disease. The 1.5 x risk value is simply 26.7 divided by 17.8. Note that this is relative risk! Not absolute risk! Increased risk does NOT mean I will get the disease.


So what is the genetic basis for this increased relative risk of getting prostate cancer? I received genetic information from my mother and father that shows, on a region on chromosome number 8 (something called band 24) from each parent, I have a certain sequence of those four chemicals mentioned above and at one specific point I have a certain chemical base (remember one from my mother and one from my father), here being G and T. We typically write this as GT and this is termed the “genotype”. People that have a T from their mother and a T from their father, with the genotype being TT have average risk for prostate cancer. However, one of my parents passed along a G, where the T would be. This is a SNP or “snip”, one chemical replacing another. It turns out that this SNP is related to an increase in the risk of prostate cancer.


How is this SNP related to increased risk of prostate cancer? This SNP (G for T on one of the number 8 chromosomes) was shown to be related to an increase risk of prostate cancer in a study of more than 2300 Caucasian males. This study is called a “Genome Wide Association Study” (GWAS...we have abbreviations for everything!)


It turns out from other studies that there are other SNPs (single base difference at other places on DNA) that have been related to increased risk for prostate cancer in middle-to-late age Caucasian males. In a study of over 3600 male Caucasians, the SNP mentioned above, along with four other SNPs (snips) and family history was related to the increased risk. So, we can say that the group of five SNPs and the family history provides the cumulative (here for discussion) risk.


Here are my genotypes for the five potential SNPs (in general terms here) making up the cumulative risk relative to the normal risk genotype:

SNP 1 (from above) – Normal risk genotype TT, my genotype GT – increased risk

SNP 2 – Normal risk genotype CC, my genotype CC – normal risk

SNP 3 – Normal risk genotypes AG or GG, my genotype AA – increased risk

SNP 4 – Normal risk genotype GT, my genotype GT – normal risk

SNP 5 – Normal risk genotype CC, my genotype CC – normal risk

Family history – unknown (I am adopted). *Update - I know some family history, but not related to prostate cancer.


So, out of the five SNPs that make up the cumulative risk, I have two SNPs that are related to increased risk.


What does this mean to me. I will talk to my doctor about this and I will look into “prostate health”. What if I did not know this information? I would follow the American Cancer Association recommendations and talked to my physician. Am I going to get prostate cancer? I do not know, but I will be diligent in my healthcare.

I hope that the presentation of the information makes sense. I went to a great deal of work to go to this level of understanding my relative risk as presented in my data. Most individuals will look at the summary data and not look at this technical level. Again risk does not mean it will happen. The genetic-based risk must be looked at in the context of overall risk that includes diet, and the environment among other potential risk factors.


What are your thoughts?

Personal Genome...The Process and Initial Thoughts

As I debated getting my genome tested, here not looking at all of the sequence of my DNA, but only some of the current variations (single nucleotide polymorphisms SNPs, pronounced snips), I went in search of the direct to consumer companies and ended up looking at three (here I am not endorsing any one of them). When I first stared looking at companies (and some have now stopped operation as direct to consumer companies) Navigenics appeared to require the testing be done through a physician or wellness program, both of which I had access to, but neither that I wanted to bother. Certainly, and I may do this, I would like to work with both my physician and wellness program as we can all move along the learning curve. Decodeme was a second company and for me at this time, for reasons you will see later, was too expensive, so I chose a third company, 23andme.


I went online, and reviewed the procedure. Here, pick the service and pay via credit card, then wait for the kit to arrive. In about a week, I received the test sample kit and promptly read the directions. Following the directions, I provided the saliva sample, which took about five minutes of spitting into the tube to obtain the correct volume. The tube cap has a preservative that automatically mixes with the saliva when you close the cap. At this point I put the shipping cap on the tube, placed it in the provided zip-lock bio-bag and placed that into the already addressed return container.


The fact that saliva was used is key to a consumer product. I think the other two services mentioned above ask for a cheek swab. With DNA in every nucleated cell (cell with a nucleus) of the body I guess it really doesn't matter...I just do not see the public drawing an arterial blood sample! And, I would struggle supplying a hair sample!


Now, at this point, I hesitated as I thought do I really want to know all this. I would receive information about my physical traits, RISK OF DISEASE, "drug sensitivity", and DISEASE CARRIER STATUS. The capital letters show the information I was questioning. Well, I though "go ahead the DNA is there regardless of whether or not I know what is says"...into the mailbox it went...I could now wait for the results, which I should see in 4 to 6 weeks.


I don't know if business was slow or if the laboratory folks were just super-efficient because I got the results in three we go!


Now some of you may be thinking let's get to the good stuff. What diseases is he at risk for, what disease does he carry to pass along...not so fast! We are going to start with the simple things, what my DNA states about my physical traits. We'll cover this over the first week or two. Take a look at "About DFK". Check the link on the menu at the left. Some questions come to mind right away: 1. I know I can taste bitter substances, my genetic make-up says otherwise. (Note to self #1 My DNA does not get it correct all the time. Note to self #2 ask 23andme for a refund!). Really, it is all relative. my DNA is not saying I absolutely will not taste bitter substances. Green eyes versus brown...My DNA states that I "Likely Brown"...well, the person who set up the 23andme automated results put in the term "likely brown" or someone did, because while DNA tells us something, it does not speak!


So why doesn't my DNA match up with my expressed trait all the time...years and years of environment plus some other reasons. Let me know what you think!

Looking at a Personal Genome. Why?

Note; This is a modification of a post from a previous blog entry.


Why is this blog here? With the responsibility of keeping our students on the forefront of pharmacy education, I felt obligated to present, from a public point of view, where "things" are at with personal genetic information. As I have talked about patients who eliminate drugs from their body slowly (poor metabolizers) versus those who remove drugs rapidly (extensive and ultra rapid metabolizers) in class for years, I felt that this needed to be placed in the context of the "bigger picture". With the advent of direct to consumer (DTC) genetic testing, I saw the opportunity to investigate the "bigger picture".


I sent my DNA sample (saliva – about a teaspoonful) to arguably the most commercial of the DTC "personal genome" companies, 23andMe so I could delve into this new world of personal genetic information.


Being in pharmacy education, I specifically was looking at this information to see the drug-genetic connections (pharmacogenetic) side of things. I wanted to know how my body handled certain drugs. This term, pharmacogenetics was defining what I wanted to know. That is, I wanted to study my genetic makeup in order predict how I would respond to certain drugs and to understand how certain drugs should be prescribed for me. We have distinguished pharmaco(drug)genetics from pharmaco(drug)genomics. Pharmacogenetics is how a single gene interacts with a drug, whereas pharmacogenomics is how our whole genome (all our DNA) interacts with a drug.


So, for the most part, I am checking my pharmacogenetics, hence this blog...but it is much bigger than just drug response. I will learn what disease risk I have, what disease(s) I may be a carrier of and what my DNA says about physical traits. The bigger picture includes legal issues, such as discrimination, ethics, healthcare, business and broader personal questions. We all need to be thinking about the use of genetic information in this era of easy access to DNA information.


For me, there is another reason for looking at this information. Being adopted, I do not know anything about my family medical history. It made sense to me to look at my ‘predisposition’ relative to disease risk. When offering a family history you should go back three generations to put in perspective potential inherited diseases and inherited risk, if you will. I could not come close to doing that, so after I see my results from the personal genome company, I can offer that to the clinicians as my family history. Update - I now have some family history information.


So, I will start with the traits my genetics says I have. Certainly, I know how I express some of the defined traits (and some, frankly, are not pretty!). It will be interesting to see if my expression of the traits, my phenotype, matches what my genetics say I should express as a trait, my genotype.


To get us all at a starting point, click on “About DFK” at the left. You will see the trait that was tested by the personal genome company, how I express that trait and I will start looking at the results and enter the results from my DNA testing. We will see if they match…and discuss why they may not!


Ok, that is the first entry for the blog. I will be putting a notice out, via email to let everyone know when I am posting comments and results of the testing. - Blog site for the course

You are at the correct site for the blog. The blogging will start September 4, 2013 after the deadline for completion of the pre-course survey. I look forward to the interaction!