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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:599.)
© 2002 American Heart Association, Inc.

Vascular Biology

Interleukin-6 -174G>C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS)

Federica Basso; Gordon D.O. Lowe; Ann Rumley; Alex D. McMahon; Steve E. Humphries on behalf of the WOSCOPS Group

From the Centre for Cardiovascular Genetics (F.B., S.E.H.), BHF Laboratories, Royal Free and University College London Medical School, London, UK, and the University Department of Medicine (G.D.O.L., A.R.), Royal Infirmary, and the Robertson Centre for Biostatistics (A.D.M.), University of Glasgow, Glasgow, UK.

Correspondence to Steve E. Humphries, PhD, Centre for Cardiovascular Genetics, BHF Laboratories, Royal Free and University College London Medical School, 5 University St, London WC1E 6JJ, UK. E-mail rmhaseh{at}ucl.ac.uk

Interleukin (IL)-6 plays an important role in the pathogenesis of coronary heart disease (CHD). Two functional polymorphisms in the IL-6 promoter have been identified (-174G>C and -572G>C), with both the rare alleles being associated with higher plasma levels of IL-6 after bypass surgery and one of them (-174G>C) associated with CHD risk. We have studied the contribution of these polymorphisms to CHD risk in the West of Scotland Coronary Prevention Study (WOSCOPS), a primary prevention trial that demonstrated the effectiveness of pravastatin in reducing morbidity and mortality from CHD. Four hundred ninety-eight cases (consisting of individuals experiencing a cardiovascular event during 4.8 years of follow-up) and 1109 controls (individuals matched for age and smoking habits) were genotyped. In the placebo group, there was no significant evidence of higher risk associated with the -174CC genotype compared with the GG+GC group. However, in the pravastatin-treated group, CC homozygotes had a significantly lower risk of CHD compared with the GG+GC placebo group (odds ratio 0.46, 95% CI 0.27 to 0.79), and this remained statistically significant after adjustment for classic risk factors. Compared with the GG+GC group, men with the CC genotype had modestly, but not significantly, higher baseline levels of IL-6, C-reactive protein, or fibrinogen but showed a significantly greater fall in LDL cholesterol with statin treatment (P=0.036). The -572G>C polymorphism was not significantly associated with any plasma trait or CHD risk. Thus, in subjects under pravastatin treatment, the -174CC genotype was associated with a lower risk of CHD. These results demonstrate the importance of the inflammatory system in determining the risk of CHD and support the nonlipid effect of statins on risk.

Key Words: interleukin-6 • genetic polymorphisms • inflammation • pravastatin • coronary heart disease

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