Summary

While an interleukin-1 receptor antagonist gene polymorphism(IL1RN-VNTR) has recently been hypothesized to be a risk factor forcoronary artery disease, no prospective data relating this polymorphismto subsequent risk of coronary events are available. We thereforeinvestigated the association between IL1RN-VNTR genotype and theincidence of myocardial infarction (MI) in a large, prospective cohortof initially healthy men. The IL1RN-VNTR was evaluated among 385MI case subjects and an equal number of age- and smoking-matchedcontrol subjects during a 12-year follow-up. Overall, the allele and genotype distributions were similar among cases and controls, both inthe total cohort and in all subgroups evaluated. All observed genotypefrequencies were in Hardy-Weinberg equilibrium. Furthermore, therelative risk in a comparison of homozygous mutant to homozygouswild-type was 0.89 (95%CI = 0.5-1.6; P = 0.9). In this large, prospectivestudy, the IL1RN-VNTR gene polymorphism is not associated withrisks of future MI. These data also highlight the importance of hypothesistesting studies in genetic epidemiology, particularly for hypothesesgenerated from small samples or post hoc subgroup analyses.