Genotype at the −174G/C Polymorphism of the Interleukin-6 Gene Is Associated With Common Carotid Artery Intimal-Medial Thickness
- 1 October 2005
- journal article
- research article
- Published by Wolters Kluwer Health in Stroke
- Vol. 36 (10), 2215-2219
- https://doi.org/10.1161/01.str.0000182254.47941.96
Abstract
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 (χ 2 1 =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.Keywords
This publication has 29 references indexed in Scilit:
- Genetic risk factors for stroke and carotid atherosclerosis: insights into pathophysiology from candidate gene approachesThe Lancet Neurology, 2004
- Measured haplotype analysis of the aldosterone synthase gene and heart sizeEuropean Journal of Human Genetics, 2003
- Interleukin-6 Promoter Polymorphism Modulates the Effects of Heavy Alcohol Consumption on Early Carotid Artery AtherosclerosisStroke, 2003
- Genetic and Environmental Contributions to Atherosclerosis Phenotypes in Men and WomenStroke, 2003
- The determination of carotid intima medial thickness in adults—a population-based twin studyAtherosclerosis, 2003
- Carotid Intima-Media Thickness Is Associated With Allelic Variants of Stromelysin-1, Interleukin-6, and Hepatic Lipase GenesStroke, 2002
- Population-Based Twin Study of the Effects of Migration From Finland to Sweden on Endothelial Function and Intima-Media ThicknessArteriosclerosis, Thrombosis, and Vascular Biology, 2002
- Merlin—rapid analysis of dense genetic maps using sparse gene flow treesNature Genetics, 2001
- The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.JCI Insight, 1998
- Primary, Secondary, and Meta-Analysis of ResearchEducational Researcher, 1976