Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease

Background-Cytokine gene variations are contributory factors in inflammator y 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)-alpha 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 popul ation (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 heal thy control subjects. IL-1RN*2 was significantly overrepresented in Sheffie ld SVD patients (34% vs 23% in patient control subjects); IL-1RN*2 homozygo tes in the SVD population (chi(2) carriage=8.490, 1 df, P=0.0036). This eff ect 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 a nd London showed a significant association with *2 (P=0.0024). No significa nt effect of genotype at TL-1RN was observed in the Sheffield or London MVD populations. Genotype distribution analysis comparing the SVD and MVD popu lations at TL-1RN showed a highly significant trend (P=0.0007) with the use of pooled data. No significant associations were seen for the other polymo rphisms. Conclusions-IL-1RN*2 was significantly associated with SVD. A difference in genetic association between SVD and MVD was also apparent.