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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:212.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Interleukin 6 –174 G/C Promoter Polymorphism and Risk of Coronary Heart Disease

Results from the Rotterdam Study and a Meta-Analysis

Mark P.S. Sie; Fakhredin A. Sayed-Tabatabaei; Hok-Hay S. Oei; André G. Uitterlinden; Hubert A.P. Pols; Albert Hofman; Cornelia M. van Duijn; Jacqueline C.M. Witteman

From the Departments of Epidemiology and Biostatistics (M.P.S.S., F.A.S.-T., H.-H.S.O., A.G.U., H.A.P.P., A.H., C.M.v.D., J.C.M.W.) and Internal Medicine (M.P.S.S., A.G.U., H.A.P.P.), Erasmus Medical Center, Rotterdam, the Netherlands.

Correspondence to J.C.M. Witteman, Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, PO Box 1738, 3000 DR Rotterdam, the Netherlands. E-mail j.witteman{at}erasmusmc.nl

Objective— Inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Interleukin (IL) 6 has many inflammatory functions, and the IL-6 –174 G/C promoter polymorphism appears to influence IL-6 levels. Findings of previous studies on the relation between this polymorphism and risk of cardiovascular diseases are inconsistent. We investigated this polymorphism in relation to risk of coronary heart disease (CHD) in a population-based study and meta-analysis.

Methods and Results— Participants (6434) of the Rotterdam Study were genotyped. Analyses on the relation between genotype and CHD were performed using Cox proportional hazards tests, and the association between genotype and plasma levels of IL-6 and C-reactive protein was investigated. All of the analyses were adjusted for age, sex, and common cardiovascular risk factors. A meta-analysis was performed, using a random effects model. No association between genotype and risk of CHD was observed. The polymorphism was not associated with IL-6 levels, but the C-allele was associated with higher C-reactive protein levels (P<0.01). Our meta-analysis did not show a significant association between the genotype and risk of CHD.

Conclusions— We conclude that the polymorphism is not a suitable genetic marker for increased risk of CHD in subjects 55 years of age.

Inflammation plays an important role in atherosclerosis. The association of the inflammatory interleukin 6 –174 G/C polymorphism and risk of coronary heart disease was investigated in a population-based study and additional meta-analysis. No association was found; we conclude the polymorphism is not a suitable marker for increased risk.

Key Words: coronary heart disease • inflammation • IL-6 • polymorphism

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