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

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.