The −589C>T polymorphism in the interleukin‐4 gene (IL‐4) is associated with a reduced risk of myocardial infarction in young individuals

Summary. Background: Inflammatory reactions contribute to the development of arterial disease. We investigated the role of interleukin‐4 (IL‐4) in the development of myocardial infarction (MI) by genotyping patients with MI and control subjects for the ?589C>T (rs2243250) single nucleotide polymorphism (SNP), which tags a functional haplotype of IL‐4. Methods and results: Study of Myocardial Infarctions Leiden (SMILE) included 560 men with a first MI and 646 control subjects. The Valencia study included 305 patients with MI at ≤52 years (men and women) and 310 control subjects. In SMILE no clear overall association with the ?589C>T genotype was found odds ratio (OR) 0.84; 95% CI 0.37–1.95 for ?589TT and 0.82; 95% CI 0.62–1.07 for ?589CT compared with ?589CC]. In patients younger than 50 years, carriership of one or two ?589T alleles was associated with a reduced risk of MI (OR 0.57: 95% CI 0.34–0.95). This result was replicated in the Valencia study, where carriers of one or two ?589T alleles had a reduced risk of MI (OR 0.67: 95% CI 0.47–0.95), with a strong protective effect of the ?598T allele in homozygous ?589T (OR 0.33: 95% CI 0.10–1.05). In the control subjects of the Valencia study, the ?589T allele was associated with reduced levels of F1+2. Conclusion: Our data indicate that the IL‐4 haplotype tagged by the ?589T allele reduces the risk of MI in young individuals.