Abstract MP071: Genetic Modification of Triggers of Acute Myocardial Infarction: Results From a Case-crossover Study in Costa Rica

Abstract

Background: Coffee intake and heavy physical exertion are triggers of acute myocardial infarction (AMI). It is hypothesized that their triggering effects can be modified by genetic variation. Methods: The study population consisted of incident cases (n=1354 for coffee intake, and n=1101 for heavy physical exertion) of nonfatal AMI recruited in Costa Rica between 1994 and 2004. Coffee intake and heavy physical exertion were assessed with validated questionnaires. Blood samples were collected and genotyping was conducted. We used a case-crossover design to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of AMI associated with each trigger stratified by the genotypes of each SNP included. Chi-square tests of homogeneity of RR across genotypic strata were used to assess effect modification by genetic factors. We included SNPs from both candidate genes (candidate SNPs) and previous genome-wide association studies (GWAS SNPs) related to the pathophysiological pathways of the triggering effects. Specifically, the candidate SNPs were from select genes related to sympathetic nervous system, renin-angiotensin system, caffeine metabolism, and habitual coffee consumption. The GWAS SNPs were those previously found to be associated with AMI/coronary artery disease, lipid metabolism, blood pressure, heart rate, blood coagulation, matrix metalloproteinase, and adhesion molecules. A p-value of 0.05 was considered statistically significant at first. We then performed Bonferroni correction and false discovery rate (FDR) adjustment to account for multiple testing. Results: Among the SNPs associated with AMI/coronary artery disease, rs10483853 significantly modified the triggering effect of coffee, and rs10507130 was significant for heavy physical exertion. Among the SNPs associated with blood pressure, rs935334 was significant for both triggers. Among the SNPs associated with heart rate, rs9398652, rs1541010 and rs1395479 were significant for coffee intake, and rs17287293 and rs223116 were significant for heavy physical exertion. Among the SNPs associated with blood coagulation, rs4460176, rs565229, and rs12367822 were significant for coffee intake, and rs2731672, rs10489087, rs647316, rs2138852, rs1473247, rs12367822 and rs1671152 were significant for heavy physical exertion. The two SNPs associated with serum matrix metalloproteinase (rs11225434 and rs495366) both significantly modified the triggering effect of heavy physical exertion. No SNPs remained statistically significant after Bonferroni correction or FDR adjustment. Conclusions: We identified several potential genetic modifiers of the triggering effects of coffee intake and heavy physical exertion on AMI. Among them, heart rate and blood coagulation traits appeared to be more important. Replication studies in other populations will help confirm and expand our findings.