Grant: Catalyst Grant: Personalized Health Catalyst Grants

Women aged 55 years and younger who suffer from acute coronary syndrome (ACS) have been known to have poorer health outcomes and higher death rates than men. Prior research has shown that women have a higher risk of major bleeds (requiring medical treatments) compared to men. Also, many drugs that are prescribed to decrease clot formation, like clopidogrel, are associated with increased risk of bleeding in women compared with men. The digestion of these drugs in humans is regulated by many genes. In particular, various CYP genes are known to play a role in the metabolism of drugs including Clopidogrel. Any mutation in these genes can alter the digestion of these drugs leading to either excessive or poor metabolism causing higher risk of either bleeding or less of a beneficial effect on the formation of clots in blood vessels. The understanding of factors underlying increased risk of bleeding in women as compared to men on these drugs is still incomplete. Therefore we propose to examine differences in drug-gene interactions between male and female clopidogrel users as a possible factor explaining these differences. We believe that interaction of the CYP genes responsible for metabolism of these drugs, in men vs. women could help explain the increased risk of major bleeding in women as compared to men. Our cohorts GENESIS-PRAXY (GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary SYndrome) and the Recurrence and inflammation in the acute coronary syndromes (RISCA) study are prospective cohorts of patients hospitalized for Acute Coronary Syndrome. We propose to enhance our PRAXY and RISCA cohorts through expanding data analysis to genotyping in order to identify differences in sequencing at the single nucleotide level. A better knowledge of these differences could lead to the development of better therapies tailored the patient sex.