Interleukin-6 gene polymorphisms and susceptibility to myocardial infarction: the ECTIM study

There is growing evidence that interleukin (IL) 6 plays an important role i n the atherosclerotic process because of its role in mediating immune and i nflammatory responses and inducing cell proliferation. The present study ex amined whether molecular variations at the IL-6 locus are involved in the p redisposition to myocardial infarction. The entire coding region, 1158 bp o f the 5' flanking region and 237 bp of the 3' flanking region of the IL-6 g ene were screened. We detected three nucleotide substitutions in the 5' reg ion at positions -174 (G/C), -572 (G/C), and -596 (G/A) from the transcript ion start site, and one insertion/deletion in the 3' region at position +52 8 after the Stop codon. These polymorphisms were (genotyped in the Etude Ca s-Temoin de l'Infarctus du Myocarde study comparing male patients (n=640) a nd age-matched controls (n=719) from Northern Ireland and France. The IL-6/ G-174C and IL-6/G-596A polymorphisms were in nearly complete association. C arriers of the IL-6/-174 C allele were more frequent in patients than in co ntrols. The population-adjusted odds ratio for myocardial infarction associ ated with genotype CC+CG vs. GG was estimated as 1.34. In French patients t he number of coronary arteries with greater than 50% stenosis was assessed by angiography. The IL-6/-174 C allele was more frequent in patients with t wo or fewer stenosed vessels than in patients with three-vessel lesions. Th ese results suggest that genetic variation at the IL-6 locus is associated with susceptibility to myocardial infarction, especially events occurring o n less extended lesions. These findings would be compatible with a lower IL -6 secretion associated with the IL-6/-174 C allele, itself or in combinati on with other promoter polymorphisms, leading to more unstable plaques.