A recent study led by Carlos Bustamante of Cornell and Sarah Tishkoff of the University of Pennsylvania has shown that genetically speaking, African American can mean a lot of different things.

The researchers and their co-workers analyzed DNA data from 365 African Americans, 203 West Africans from 12 different countries, and 400 Europeans from 42 countries.  Their results, published in the Proceedings of the National Academy of Sciences, show that the average amount of DNA in an African American’s genome that could be traced back to West Africa was about 77%, but ranged from as little as one percent to as much as 99%.

These findings have important implications not only for understanding the ancestry of African Americans and the history of human migrations, but also for medical treatment.

“That some individuals who self-identify as African American show almost no West African ancestry and others show almost complete West African ancestry has implications for pharmacogenomics studies and assessment of disease risk… caution should be used in prescribing treatment based on differential guidelines for African Americans, ” the authors write.

The researchers also undertook an analysis to determine if any particular stretches of DNA found in African Americans were more often descended from their West African ancestors.  The strongest finding was that there are elevated levels of African ancestry on the X chromosome, most likely reflecting a history in which interracial mating primarily happened between mothers with African ancestry and fathers with European ancestry.

The African groups studied by the research team represent just a few of the ten ethnicities mentioned most often in slave trade records. Future studies might examine other relevant populations from Sierra Leone, Senegal, Guinea Bissau, and Angola, providing further insights into the genetic ancestry of African Americans.

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Medco Health Solutions, Inc., announced this week that it will conduct a clinical trial to assess whether clopidogrel bisulfate (Plavix®, Bristol-Myers Squibb and Sanofi-aventis) is just as effective as the newer drug prasugrel (Effient™, Eli Lilly and Company) in people who lack a genetic variation that inhibits their metabolism of clopidogrel. This new research has important implications for both patient safety and health care costs.

Both clopidogrel and prasugrel are anti-platelet medications that reduce the ability of blood to form clots. The drugs are used to reduce the risk of a heart attack and stroke in people who have suffered from a recent cardiovascular event, and in those who have peripheral artery disease, unstable angina or a stent.

Variations in the CYP2C19 gene that prevent clopidogrel from being converted into its active form in the body have been shown to prevent patients from receiving the drug’s full benefit. People with these gene variations who are taking clopidogrel may be at a higher risk for heart attacks, strokes and death from cardiovascular causes than those whose genetics allow them to metabolize the drug.

(Prasugrel is metabolized through a different biological pathway than clopidogrel, and is not affected by CYP2C19 variants.)

23andMe customers can see their data for several important CYP2C19 variations in the ‘Clopidogrel (Plavix®) Efficacy’ Clinical Report.

Medco’s study will assess patients’ rates of nonfatal heart attacks, nonfatal strokes and cardiovascular deaths after six months of treatment with either clopidogrel or prasugrel. Researchers will be looking to see if there is any difference between those patients who are taking clopidogrel, and whose genetics predict that they should be able to metabolize it—and those patients who are taking prasugrel.

“Plavix is going generic in 2011 and if found to be equally effective as Effient for patients who have a normally functioning version of the CYP2C19 gene, the study provides the evidence that would allow these patients to opt for a lower cost treatment,” said Medco’s chief medical officer Dr. Robert Epstein in a press release.

Former U.S. Secretary of Health and Human Services Michael O. Leavitt was quoted in the Medco press release as saying, “Studies like this are necessary to show how innovation can derive greater value from what we spend on health care.  A simple test can identify a drug’s ability to work for a particular patient or point them to another one that could provide a better outcome. Personalized medicine is the new frontier in making medication safer and more effective. What we learn from this study, and others like it, will save lives and money.”

Patients aren’t the only ones who would save if Medco’s research shows that the soon-to-be generic clopidogrel is an effective choice for them. An Associated Press story notes that generic drugs are more profitable for Medco than higher-priced brand name products.

Comparative effectiveness research has received a lot of attention in the United States health care debate lately.  Some worry that it will result in policies that are not in patients’ best interests.

“We need to be mindful of the goal of comparative effectiveness research and not lose all that we have gained in understanding how individuals differ and how that could be factored into better diagnostics and preventive strategies,” said National Institutes of Health (NIH) director Francis Collins, speaking at a recent American Association for the Advancement of Science forum on personalized medicine.

Collins recommended that genetic factors be included in comparative effectiveness research (as is the case in Medco’s study), to make sure that treatments that work for specific groups of patients are not “lost in the wash by considering everybody equivalent.”

The Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (GeCCO) is part of Medco’s “Genetics for Generics” program and is registered with the NIH.

Related Spittoon Posts:
More Evidence that Genetics Can Reduce the Efficacy of Anti-Clotting Medication Clopidogrel
SNPwatch: Genetic Variants May Reduce Ability of Anti-Clotting Drug Clopidogrel to Prevent a Second Heart Attack

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Researchers are sometimes frustrated when a prospective drug proves effective in some patients, but not enough to justify giving it to everyone who has the condition it is intended to treat.

The beta-blocker drug bucindolol met that fate in 2001 when it was originally tested as a treatment for heart failure. Though it did help a fraction of the 2,708 patients in the study, it didn’t improve the condition of enough patients to be approved for the market.

But now researchers have rescued bucindolol from the pharmaceutical dustbin by identifying a genetic variation that increases a person’s chances of benefiting from the drug. Researchers collected DNA samples from 1,040 patients who were involved in the original study, and found that genetics plays a significant role in determining its effectiveness. In light of the discovery, the company that owns the drug, ARCA biopharma, has applied to the FDA for approval to sell it.

The most important gene in determining bucindolol’s effectiveness is ADRB1, which is not surprising — the gene is involved in activating the “fight or flight” response to the hormone adrenaline. Beta-blocker drugs such as bucindolol suppress that response, protecting a weak heart from the strain that an adrenaline response produces.

It appears that bucindolol blocks adrenaline’s effects only if a person has a particular form of the ADRB1 gene. Among those people, bucindolol decreased the risk of death from heart-related causes 48%.

23andMe customers can determine whether they have the form of ADRB1 that responds to bucindolol by checking their genotypes at the SNP rs1801253; the CC genotype is the responsive form of the gene. 23andMe customers and demo account holders can also read more about bucindolol in the Beta-blocker Response section of My Health and Traits.

Until now, the vast majority of drugs prescribed on the basis of genetics have been for cancer — and their effectiveness has mostly depended on the genetics of the tumor rather than the patient. But the bucindolol story illustrates the broader promise of genetic information for drug developers, physicians and patients. The hope is that eventually, understanding how genetic variations influence the effectiveness of drugs and their side effects will usher in a new era of personalized medicine.

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