Genetic variants within the interleukin-1 gene cluster, and risk of incident myocardial infarction, and ischemic stroke: A nested case-control approach

Background and purpose Recent findings implicating specific gene polymorphisms of the interleukin-1 superfamily gene cluster in the risk of developing athero-thrombotic disorders have generated great interest. However, to date, no prospective, genetic–epidemiological data are available. Methods Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated seven gene polymorphisms within the interleukin-1 gene cluster among 599 individuals who subsequently developed athero-thrombotic event and among 599 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up (341 incident myocardial infarction matched case-control pairs and 258 incident ischemic stroke matched case-control pairs). Results Overall, we observed little evidence of association between the polymorphisms tested and risk of incident athero-thrombotic events. Further adjustment for traditional cardiovascular risk factors yielded similar null findings. Of note, a modest association of rs1143623 with reduced risk of incident MI was found (recessive model: OR = 0.455, 95% CI = 0.215–0.960, uncorrected p = 0.039). However, this finding was not corrected for multiple testing, and thus requires cautious interpretation. Conclusion In contrast to prior retrospective studies, our prospective data suggest that the IL-1 cluster gene variation is not associated with risk of athero-thrombotic disorders.