Synergistic contribution of CD14 and HLA loci in the susceptibility to Buerger disease
Synergistic contribution of CD14 and HLA loci in the susceptibility to Buerger disease
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DOI：
10.1007/s00439-007-0408-1
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发表时间：
2007-11-01
期刊：
影响因子：
5.3
通讯作者：
Kimura, Akinori
中科院分区：
文献类型：
--
作者：
Chen, Zhiyong;Takahashi, Megumi;Kimura, Akinori
伯格病是一种病因不明的隐匿性血管疾病。虽然吸烟是BD的一个众所周知的危险因素，但遗传因素也可能在病因学中发挥作用。由于慢性细菌感染（如口腔牙周炎）可能参与了BD的发病机制，因此参与感染性免疫的基因多态性可能作为遗传因素与BD相关。我们以前曾报道HLA-DRB 1 *1501和B54与日本BD相关。本研究分析了131例日本BD患者和227例健康对照者的HLA-DPB 1、DRB 1和B基因多态性。此外，我们研究了细菌脂多糖的主要受体CD 14的功能性启动子多态性，-260 C > T。结果发现，CD 14 TT基因型频率[37.4 vs.24.2%，P = 0.008 OR = 1.87，95%可信区间（CI; 1.18，2.97）]、DRB 1 *1501（34.4 vs. 13.2%，P（c）= 4.4 x10（-5），OR = 3.44，95%CI; 2.06，5.73）和DPB 1 *0501（79.4 vs. 55.1%，P（c）= 4.7 x10（-5），OR = 3.14，95%CI; 1.93，5.11）在患者中显著高于对照组，表明至少有三种遗传标记与BD相关。这些相关标记的分层分析表明遗传因素的协同作用。携带这三种标记物中任何两种的个体的优势比范围为4.72至12.57。提示BD的易感性部分受先天免疫和获得性免疫相关基因控制。
Buerger disease (BD) is an occulusive vascular disease of unknown etiology. Although cigarette smoking is a well-known risk factor of BD, genetic factors may also play a role in the etiology. Because chronic bacterial infection such as oral periodontitis is suggested to be involved in the pathogenesis of BD, gene polymorphisms involved in the infectious immunity might be associated with BD as the genetic factor(s). We have previously reported that HLA-DRB1*1501 and B54 was associated with BD in Japanese. In this study, polymorphisms in HLA-DPB1, DRB1 and B were analyzed in 131 Japanese BD patients and 227 healthy controls. In addition, we investigated a functional promoter polymorphism, -260 C > T, of CD14 that is a main receptor of bacterial lipopolysaccharide. It was found that the frequencies of CD14 TT genotype [37.4 vs. 24.2%, P = 0.008 OR = 1.87, 95% confidence interval (CI); 1.18, 2.97], DRB1*1501 (34.4 vs. 13.2%, P (c) = 4.4 x10(-5), OR = 3.44, 95%CI; 2.06, 5.73) and DPB1*0501 (79.4 vs. 55.1%, P (c) = 4.7 x10(-5), OR = 3.14, 95%CI; 1.93, 5.11) were significantly higher in the patients than in the controls, demonstrating that at least three genetic markers were associated with BD. Stratification analyses of these associated markers suggested synergistic roles of the genetic factors. Odds ratios ranged from 4.72 to 12.57 in individuals carrying any two of these three markers. These findings suggested that the susceptibility to BD was in part controlled by genes involved in the innate and adaptive immunity.