A new report in the Journal of the American Medical Association adds to the mounting evidence that genetic variations impact the efficacy of clopidogrel (Plavix®), a drug used to prevent blood clots in people who have had a heart attack or stroke and also those with peripheral artery disease and unstable angina.

Previous research has shown that certain variations in the CYP2C19 gene prevent the body from converting clopidogrel into its active form. That reduces the amount of anti-clotting effect people get from the medication, increasing their risk for heart attacks, strokes and death from cardiovascular causes.

(23ndMe customers can learn how their data fits in with this research in a previous Spittoon post or in the Clopidogrel Efficacy Drug Response Report.)

The researchers, led by Alan Shuldiner of the University of Maryland School of Medicine, determined that BMI, lipid levels and age account for about 10% of the variation in clopidogrel’s ability to prevent blood clotting. Variation in the CYP2C19 gene accounted for another 12%, meaning that other factors, probably both genetic and non-genetic, are also at work.

For patients whose genetics may reduce the benefits of clopidogrel treatment, there are other options. Prasugrel (Effient®) was recently approved by the FDA and appears not to be affected by the same variations that impact clopidogrel efficacy, although there are some concerns about bleeding caused by this drug.  Several other drugs (ticagrelor, cangrelor, elinogrel) that could be used for clotting reduction in place of clopidogrel are currently in clinical trials.

Clinical trials have not yet been conducted to show if identifying people with variants of the CYP2C19 before prescribing clopidogrel actually improves health outcomes.  If such studies do show a benefit and this type of testing becomes routine, people with these variants might be steered away from clopidogrel by their doctors, which would seem to be a boon for the makers of newer medications.

But in an editorial accompanying the study in JAMA, Deepak Bhatt suggests that testing for these variations would also allow physicians to know for whom clopidogrel will work (probably). This would be an important piece of information considering that the patent on clopidogrel is set to expire in 2011, so cheaper generic forms of the drug will be available then.

“Although such testing currently is expensive, the cost will decrease and hopefully will coincide with supportive data.  Furthermore, if such testing allowed use of a less expensive generic anitplatelet drug, the test might essentially pay for itself,” he writes.

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A new discovery could someday help identify smokers at risk for chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States.

More than 12 million people in the U.S. have been diagnosed with COPD, and another 12 million may have the condition and not know it.  These people have difficulty breathing due to excessive inflammation in their lungs that has narrowed their airways.  The cause of the inflammation is usually prolonged exposure to an inhaled irritant, most often cigarette smoke. Nine out of ten COPD deaths can be attributed to smoking.

But even though most people with COPD are current or former smokers, not every smoker gets COPD.  Only about 20% will develop the disease, suggesting that there might be genetic factors that make some smokers more susceptible than others. New research, published yesterday in the journal PLoS Genetics, suggests that variation in a genetic region on chromosome 15 previously linked to nicotine addiction, lung cancer and peripheral artery disease might also increase the risk for COPD.  In light of the mounting evidence for the importance of this stretch of DNA, the authors of the new report suggest that genetic screening of smokers in order to find those at the highest risk may be an attractive interventional strategy.

Sreekumar Pillai, a scientist at GlaxoSmithKline, and colleagues from several research institutions studied a total of more than 5,000 people with European ancestry and found that each A at the SNP rs1051730 on chromosome 15 increased odds of COPD by about 1.3 times.  They also found that each C at SNP rs8034191 increased the odds of COPD by about 1.4 times. The two SNPs are very close to each other and probably both mark the same variation affecting COPD risk, although the authors did not test this.

[23andMe customers can check their data for rs1051730 and rs8034191 using the Browse Raw Data feature.  Keep in mind that because the SNPs are closely linked, having the same version of both (either non-risk or risk) is expected.  A riskier version at both does not indicate doubled risk.]

Research has shown that in smokers, each A at rs1051730 is associated with smoking one more cigarette per day.  Whether rs1051730 is linked to lung cancer and peripheral artery disease because of or in addition to its effects on smoking has been controversial.  The authors of the current study say that while their data does not allow them to solve this dilemma with regard to the effects of the chromosome 15 SNPs on COPD, several aspects of their study indicate that the genetic variation has a direct effect on the disease, independent of smoking behavior.

The authors do note, however, that in some subsets of their study population the effect of the riskier versions of the genetic variations was greater in current smokers compared to former smokers.  This could mean that people who have a harder time quitting are more likely to develop COPD.  Alternatively, it could be the case that some people are at higher risk for COPD if they continue to smoke.

The researchers also found evidence for variations contributing to COPD on chromosome 4, although the results were not statistically significant. However, this same region of DNA was correlated with lung function in a different report in same issue of PLoS Genetics.  Both research groups pointed out that the nearest gene to the chromosome 4 variations they identified is involved in lung development, suggesting that future research targeting these variations might reveal more insight into COPD and other lung diseases.

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