Abstract P414: Omega-3 Fatty Acids Modify the Genetic Risk of Early Onset Acute Coronary Syndrome

Abstract

Background: Recent gene-environment interaction studies suggest that diet may influence an individual’s genetic predisposition to cardiovascular risk. We tested the hypothesis that omega-3 fatty acid intake may influence the risk for acute coronary syndrome (ACS) conferred by genetic polymorphisms among patients with premature ACS. Methods: Our study population consisted of 706 patients of white European descent enrolled in GENESIS PRAXY, a multicentre prospective cohort study of patients aged 18 to 55 years hospitalized with ACS. We used a case-only design to investigate gene-environment interactions between the omega-3 index (a validated biomarker of omega-3 fatty acid intake) and 30 single nucleotide polymorphisms (SNPs) that have been robustly associated with ACS. We used logistic regression to study the associations between each SNP and the omega-3 index. Interaction was also assessed between the omega-3 index and a genetic risk score generated from the 30 SNPs as a simple unweighted count of the risk alleles for each SNP. All the SNPs used in the genetic risk score were uncorrelated (r2 <0.3). We further adjusted all models for age and sex. Results: The median age of our population was 49 years and 72.1% were male. Median omega-3 index was 3.35% (interquartile range 2.81-4.07%). None of the SNPs deviated from Hardy-Weinberg equilibrium. A synergistic multiplicative interaction for increased ACS risk was found between carriers of chromosome 9p21 variant rs4977574 and low omega-3 index (OR 1.57, 95% CI 1.07-2.32, p=0.02), but did not reach significance after correction for multiple testing. Similar results were obtained in the adjusted model (OR 1.55, 95% CI 1.05-2.29, p=0.03). We did not observe interaction between the genetic risk score and the omega-3 index. Conclusions: In conclusion, our results suggest that omega-3 fatty acid intake may modify the genetic risk conferred by chromosome 9p21 variation among ACS patients but require independent replication in other cohorts. Further validation research is also warranted to examine whether this interaction occurs in other ethnic groups.