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(Stroke. 2005;36:2215.)
© 2005 American Heart Association, Inc.

Original Contributions

Genotype at the –174G/C Polymorphism of the Interleukin-6 Gene Is Associated With Common Carotid Artery Intimal-Medial Thickness

Family Study and Meta-Analysis

Bongani M. Mayosi, DPhil; Peter J. Avery, PhD; Michelle Baker, MSc; Nicole Gaukrodger, BSc; Helen Imrie, PhD; Fiona R. Green, PhD; Martin Farrall, MBChB; Hugh Watkins, MD, PhD Bernard Keavney, DM

From the Department of Cardiovascular Medicine (B.M.M., F.R.G., M.F., H.W.), University of Oxford, Oxford, United Kingdom; The Cardiac Clinic (B.M.M.), Department of Medicine, University of Cape Town, South Africa; School of Mathematics and Statistics (P.J.A.) and Institute of Human Genetics (M.B., N.G., H.I., B.K.), University of Newcastle upon Tyne, United Kingdom.

Correspondence to Bongani M. Mayosi, The Cardiac Clinic, E25 Groote Schuur Hospital, Anzio Road, Observatory 7925, South Africa. E-mail bmayosi{at}uctgsh1.uct.ac.za

Background and Purpose— Studies in unrelated individuals have produced conflicting findings concerning the putative association between the interleukin-6 (IL-6) –174G/C polymorphism and carotid intimal-medial thickness (IMT). We have used a family-based genetic association design to assess the heritability of carotid IMT and to investigate the hypothesized association of carotid IMT with the IL-6 to –174G/C polymorphism.

Methods— We studied 854 members of 224 white British families. The heritability of carotid IMT was determined using Multipoint Engine for Rapid Likelihood Inference. Genetic association analyses were carried out using ANOVA and family-based tests of association implemented in Quantitative Transmission Disequilibrium Test. A meta-analysis of previous studies of the association was conducted to place our result in context.

Results— The heritability of carotid IMT was 24%. Under a recessive model (GG+GC versus CC), there was significant evidence of association between IL-6 to the –174G/C genotype and adjusted log_e maximal carotid IMT (F=5.469; P=0.02). Family-based analyses using Quantitative Transmission Disequilibrium Test showed no evidence of population stratification as a cause of the observed association (²₁=0.469; P=0.4934). The CC genotype was associated with a 4.8% increase in maximal carotid IMT and accounted for 0.6% of the observed variation in the trait, which is equivalent to 2.5% of the heritable component. A meta-analysis of the present and 2 previous large studies, which enrolled a total of 2930 subjects, confirmed the recessive effect of the C allele on carotid IMT (P=0.0014).

Conclusions— The genotype at the IL-6 to –174G/C polymorphism is associated with common carotid artery IMT, although the size of the genetic effect is small.

Key Words: atherosclerosis • carotid arteries • carotid intimal medial thickness • genetics