PADI4 polymorphism predisposes male smokers to rheumatoid arthritis
PADI4 polymorphism predisposes male smokers to rheumatoid arthritis
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DOI：
10.1136/ard.2010.130526
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发表时间：
2011-03-01
影响因子：
27.4
通讯作者：
Yamamoto, Kazuhiko
中科院分区：
文献类型：
--
作者：
Kochi, Yuta;Thabet, Mohamed M.;Yamamoto, Kazuhiko
目的探讨类风湿关节炎(RA)患者中肽精氨酸脱亚氨酶4(PADI4)基因多态性在亚洲和欧洲人群中的差异，分析PADI4基因多态性与性别、吸烟状况之间可能存在的基因环境交互作用。方法采用Sequenom MassARRAY软件，对3组独立的病例对照样本(第一组，1019例RA患者，907例对照；第二组，999例RA患者，1128例对照)进行PADI4基因分型。结果在第一组日本样本中，PADI4基因多态性(Rs1748033)比女性和从不吸烟者(OR(等位基因)1.25；95%CI1.02~1.53；p(趋势)=0.032)具有更高的危险性。此外，男性吸烟者的风险最高(OR(等位基因)1.46；95%CI 1.12~1.9；p(趋势)=0.0047)。结论PADI4基因多态性是男性吸烟者患类风湿性关节炎的高危因素，亚洲人群和欧洲人群间的遗传差异可能是男性吸烟率差异的部分原因。
Objective To elucidate the differential role of peptidyl arginine deiminase 4 (PADI4) polymorphism in rheumatoid arthritis (RA) between Asian and European populations, possible gene-environmental interactions among the PADI4 polymorphism, sex and smoking status were analysed.Methods Three independent sets of case-control samples were genotyped for single-nucleotide polymorphisms in PADI4; Japanese samples (first set, 1019 RA patients, 907 controls; second set, 999 RA patients, 1128 controls) using TaqMan assays and Dutch samples (635 RA patients, 391 controls) using Sequenom MassARRAY platform. The association of PADI4 with RA susceptibility was evaluated by smoking status and sex in contingency tables and logistic regression models.Results In the first set of Japanese samples, PADI4 polymorphism (rs1748033) showed a greater risk in men (OR(allele) 1.39; 95% CI 1.10 to 1.76; p(trend) = 0.0054) than in women and in ever-smokers (OR(allele) 1.25; 95% CI 1.02 to 1.53; p(trend) = 0.032) than in never-smokers. Moreover, the highest risk was seen in male ever-smokers (OR(allele) 1.46; 95% CI 1.12 to 1.90; p(trend) = 0.0047). Similar trends were observed in the second set of Japanese samples as well as in Dutch samples.Conclusion PADI4 polymorphism highly predisposes male smokers to RA, and the genetic heterogeneity observed between Asian and European populations may be partly explained by differences in smoking prevalence among men.