Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis.
Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis.
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DOI：
10.1136/ard.2010.130138
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发表时间：
2011-03
影响因子：
27.4
通讯作者：
Rueda B
中科院分区：
文献类型：
--
作者：
Diaz-Gallo LM;Gourh P;Broen J;Simeon C;Fonollosa V;Ortego-Centeno N;Agarwal S;Vonk MC;Coenen M;Riemekasten G;Hunzelmann N;Hesselstrand R;Tan FK;Reveille JD;Assassi S;García-Hernandez FJ;Carreira P;Camps MT;Fernandez-Nebro A;de la Peña PG;Nearney T;Hilda D;González-Gay MA;Airo P;Beretta L;Scorza R;Herrick A;Worthington J;Pros A;Gómez-Gracia I;Trapiella L;Espinosa G;Castellvi I;Witte T;de Keyser F;Vanthuyne M;Mayes MD;Radstake TR;Arnett FC;Martin J;Rueda B
PTPN 22基因中的两个功能性单核苷酸多态性（SNP）（rs 24746601和rs33996649）与自身免疫相关。本研究的目的是首次研究R263 Q SNP的作用，并重新评估R620 W SNP在系统性硬化症（SSc）易感性和临床表型遗传易感性中的作用。3422例SSc患者（2020例局限性皮肤SSc和1208例弥漫性皮肤SSc）和3638例来自西班牙初始病例对照组的高加索血统健康对照和7个额外的独立重复队列被纳入我们的研究。采用TaqMan等位基因识别试验对PTPN 22基因rs33996649和rs 2476601多态性进行基因分型。进行荟萃分析以测试这些PTPN 22多态性在SSc中的总体效果。荟萃分析显示rs 2476601 T等位基因与SSc易感性相关的证据（pFDR校正=0.03汇总，OR 1.15，95% CI 1.03 - 1.28）。此外，rs 2476601 T等位基因与抗着丝粒阳性状态显著相关（pFDR校正=0.02汇总，OR 1.22，95% CI 1.05至1.42）。尽管rs33996649 A等位基因与西班牙人群中的SSc显著相关（pFDR校正=0.04，OR 0.58，95% CI 0.36 - 0.92），但该相关性在荟萃分析中未得到证实（p=0.36汇总，OR 0.89，95% CI 0.72 - 1.1）。该研究表明PTPN 22 R620 W多态性影响SSc遗传易感性，但新的R263 Q遗传变异不影响SSc遗传易感性。这些数据加强了R620 W突变是自身免疫性疾病常见风险因素的证据。
Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (pFDRcorrected=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (pFDRcorrected=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (pFDRcorrected=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.
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作者：
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