Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases

• Published in: Human molecular genetics Vol. 16; no. 6; pp. 592 - 599
• Main Authors: Oda, Kanae, Tanaka, Noriko, Arai, Tomio, Araki, Jungo, Song, Yixuan, Zhang, Ling, Kuchiba, Aya, Hosoi, Takayuki, Shirasawa, Takuji, Muramatsu, Masaaki, Sawabe, Motoji
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15-03-2007; Oxford Publishing Limited (England)
• Subjects: Aged; Asian Continental Ancestry Group - genetics; Atherosclerosis (general aspects, experimental research); Atherosclerosis - genetics; Autopsy; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cytokines - genetics; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Humans; Interleukin-10 - genetics; Interleukin-1beta - genetics; Japan; Medical sciences; Molecular and cellular biology; Polymorphism, Single Nucleotide; Risk Factors; Transforming Growth Factor beta1 - genetics; Tumor Necrosis Factor-alpha - genetics; Japan; Vascular disease; Sensitivity; Autopsy; Antiinflammatory agent; Atherosclerosis; Cytokine; Cardiovascular disease; Genetics; Polymorphism
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddl483

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. We investigated the relationship of nine common single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-10, IL-4 and transforming growth factor (TGF)-β1 with the atherosclerotic severity in 10 different arteries based on 1503 consecutive autopsies of elderly Japanese subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study. The −1031C allele of TNF-α 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-1β and the +29T of TGF-β1 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. Functional SNPs in TNF-α, IL-1β and TGF-β1 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.