Interleukin-1 Receptor Antagonist Gene Polymorphism and Coronary Artery Disease

Abstract

Background —Cytokine gene variations are contributory factors in inflammatory pathology. Allele frequencies of interleukin (IL)-1 cluster genes [IL-1A(-889), IL-1B(-511), IL-1B(+3953), IL-1RN Intron 2 VNTR] and tissue necrosis factor (TNF)-α gene [TNFA(-308)] were measured in healthy blood donors (healthy control subjects), patients with angiographically normal coronary arteries (patient control subjects), single-vessel coronary disease (SVD), and those with multivessel coronary disease (MVD). Methods and Results —Five hundred fifty-six patients attending for coronary angiography in Sheffield were studied: 130 patient control subjects, 98 SVD, and 328 MVD. Significant associations were tested in an independent population (London) of 350: 57 SVD, 191 MVD, and 102 control subjects. IL-1RN*2 frequency in Sheffield patient control subjects was the same as in 827 healthy control subjects. IL-1RN*2 was significantly overrepresented in Sheffield SVD patients (34% vs 23% in patient control subjects); IL-1RN*2 homozygotes in the SVD population (χ 2 carriage=8.490, 1 df , P =0.0036). This effect was present though not quite significant in the London population ( P =0.0603). A summary trend test of the IL-1RN SVD genotype data for Sheffield and London showed a significant association with *2 ( P =0.0024). No significant effect of genotype at IL-1RN was observed in the Sheffield or London MVD populations. Genotype distribution analysis comparing the SVD and MVD populations at IL-1RN showed a highly significant trend ( P =0.0007) with the use of pooled data. No significant associations were seen for the other polymorphisms. Conclusions —IL-1RN*2 was significantly associated with SVD. A difference in genetic association between SVD and MVD was also apparent.