title: Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases.
abstract: 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-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, IL-4 and transforming growth factor (TGF)-beta1 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-alpha 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-1beta and the +29T of TGF-beta1 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-alpha, IL-1beta and TGF-beta1 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.
authors.affiliation: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Oda
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Jungo
authors.initials: J
authors.lastname: Araki
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Song
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Aya
authors.initials: A
authors.lastname: Kuchiba
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D001344:Autopsy; D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D007564:Japan; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10