Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases
Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases
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DOI：
10.1093/hmg/ddl483
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发表时间：
2007-03-15
影响因子：
3.5
通讯作者：
Sawabe, Motoji
中科院分区：
文献类型：
--
作者：
Oda, Kanae;Tanaka, Noriko;Sawabe, Motoji
动脉粥样硬化是动脉壁内膜的一种慢性炎症性疾病，细胞因子在其发病机制中起着至关重要的作用。然而，细胞因子基因的遗传变异是否会影响动脉粥样硬化的发展，这一问题的研究很少。我们研究了肿瘤坏死因子- α (tnf - α)、白细胞介素(IL)-1 β、IL-10、IL-4和转化生长因子(TGF)- β 1中9个常见的单核苷酸多态性（snp）与10种不同动脉粥样硬化严重程度的关系，基于1503例登记在日本老年研究（JG-SNP）研究中的老年日本受试者的连续尸检。tnf - α -1031C等位基因是颈动脉、股动脉和颅内动脉粥样硬化的重要保护因子[比值比（OR）分别为0.72、0.73和0.70]。IL-1 β的-511T和tgf - β 1的+29T是锁骨下动脉和颅内动脉粥样硬化的重要危险因素（OR分别为1.35和1.48）。相比之下，动脉粥样硬化的传统危险因素，如高血压和糖尿病，几乎对所有动脉都有独立的危险。tnf - α、IL-1 β和tgf - β 1基因的功能snp在动脉粥样硬化中发挥作用，尽管它们的影响不如传统危险因素那么明显，而且似乎仅限于日本老年人的特定动脉。
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)-1 beta, IL-10, IL-4 and transforming growth factor (TGF)-beta 1 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-1 beta and the +29T of TGF-beta 1 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-1 beta and TGF-beta 1 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.