Human Molecular Genetics Advance Access published online on January 9, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddl483
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© The Author 2007. Published by Oxford University Press. All rights reserved
Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1,503 consecutive autopsy cases.
1 Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 101-0062, Japan 2 Department of Clinical Bioinformatics, Graduate School of Medicine, University of Tokyo, Tokyo, 113-0033, Japan 3 Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, 173-0015, Japan 4 Department of Advanced Medicine, National Center for Geriatrics and Gerontology, Aichi, 474-8511, Japan 5 Research Team for Molecular Biomarkers, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan
* Corresponding author: Masaaki Muramatsu (E-mail: muramatsu.epi{at}mri.tmd.ac.jp), 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan. Tel: +81-03-5280-8060, Fax: +81-03-5280-8061
Received October 28, 2006; Revised December 28, 2006; Accepted December 28, 2006
BACKGROUND: Atherosclerosis is a chronic inflammatory disease in the intima of the arterial wall, where cytokines play a crucial role in the pathogenesis of this disease. However, the question of whether or not genetic variations in the cytokine genes could influence the development of atherosclerosis has been poorly investigated.
METHODS: We investigated the relationship of nine common single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-
(TNF-), interleukin (IL)-1ß, IL-10, IL-4 and transforming growth factor (TGF)-ß1 with the atherosclerotic severity in 10 different arteries based on 1,503 consecutive autopsies of elderly Japanese subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study.
RESULTS: The -1,031C allele of TNF- was a significant protective factor for atherogenesis in the carotid, femoral and intracranial arteries (odds ratio [OR]: 0.72, 0.73, and 0.70, respectively). The -511T of IL-1ß and the +29T of TGF-ß1 were significant risk factors for atherogenesis in the subclavian and intracranial arteries (OR: 1.35 and 1.48, respectively). In contrast, conventional risk factors for atherogenesis, such as hypertension and diabetes mellitus, conferred independent risks for almost all arteries.
CONCLUSIONS: Functional SNPs in TNF-, IL-1ß and TGF-ß1 genes play a role in atherogenesis, although their influences are less pronounced than those of conventional risk factors and appear to be limited to specific arteries in the Japanese elderly.