SNPWatch: Variants Associated with Clopidogrel Efficacy and Stent Thrombosis

Bakers know that some recipes are more complicated than others; some recipes require numerous ingredients, exact measurements and careful preparation, while others, such as my favorite peanut butter and jelly sandwich “recipe,” require very little. Similarly, some medical conditions are influenced by more factors than others. Last week a team of researchers, led by Drs. Guillaume Cayla and Jean-Phillipe Collet of the Centre Hospitalo-Universitaire Nímes in France, published a study in the Journal of the American Medical Association showing that many different factors, including genetics, contribute to risk for early stent thrombosis, a deadly complication to a coronary artery treatment.

Stents are small, man-made tubes inserted into constricted arteries and are a common treatment for those at risk for heart attacks due to plaque build-up along artery walls. Unfortunately, in a small number of cases, blood clots form around these stents, a condition known as stent thrombosis. Thanks to the use of anticlotting medications, stent thrombosis occurs rarely; only 0.5% to 4% of stent patients experience clotting within the first year, and most of these clotting events occur within the first month. Dr. Cayla, Dr. Hulot and their team of researchers show that the most accurate predictions of who will develop early stent thrombosis depend on both genetic and non-genetic risk factors. The most important non-genetic risk factors they found included diabetes, previous heart attack, stent diameter, and initial dosage of clopidogrel (an anticlotting medication).

While these non-genetic factors are useful in predicting early stent thrombosis, the best predictions also included information about variations in the CYP2C19, ABCB1, and ITGB3 genes. Variants in the CYP2C19 gene affect how people metabolize clopidogrel, and Cayla’s team found that those who metabolized clopidogrel faster were less likely to develop early stent thrombosis. Similarly, ABCB1 gene encodes a protein that effects clopidogrel absorption; the researchers found that individuals with the AA genotype at in the ABCB1 gene had 2.6 times higher odds of developing early stent thrombosis over individuals with the AG or GG genotypes. The gene ITGB3 encodes a protein that is important in some of the last steps of blood clotting, and they found that the C variant of was associated with lower odds of early stent thrombosis.

(23andMe customers can look up their data for and using the Browse Raw Data feature, and their drug response to clopidogrel in the Clopidogrel (Plavix®) Efficacy Established Research report.)

Knowing the right “recipe” of risk factors for early stent thrombosis is useful in predicting and, thus, preventing this serious complication, and this paper presents some potentially important ingredients. Nevertheless, more research is still needed to confirm the suggestive evidence for the contribution of ABCB1 and ITGB3 variation to risk for stent thrombosis. In addition, since this study used subjects of European descent, studies are needed to investigate whether these factors are also predictive of early stent thrombosis in other populations.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who purchased prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will not. Those customers will have access to ancestry information as well as access to their uninterpreted raw data.

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