Differential Association of Two PTPN22 Coding Variants with Crohn's Disease and Ulcerative Colitis
Differential Association of Two PTPN22 Coding Variants with Crohn's Disease and Ulcerative Colitis
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DOI：
10.1002/ibd.21630
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发表时间：
2011-11-01
影响因子：
4.9
通讯作者：
Martin, Javier
中科院分区：
文献类型：
--
作者：
Diaz-Gallo, Lina-Marcela;Espino-Paisan, Laura;Martin, Javier
背景：PTPN 22基因是人类自身免疫的重要危险因素。本研究的目的是首次评估R263 Q PTPN 22多态性在溃疡性结肠炎（UC）和克罗恩病（CD）中的作用，并重新评估R620 W PTPN 22多态性与这两种疾病的相关性。共1677例UC患者，1903例CD患者，和3111名健康对照，来自西班牙高加索血统的初始病例对照组和两个独立的欧洲血统样本组（荷兰和新西兰）被纳入研究。使用TaqMan SNP分析对R263 Q（rs33996649）和R620 W（rs 2476601）PTPN 22多态性进行基因分型。对6977例CD患者、5695例UC患者和9254例对照者进行了荟萃分析，以检验R620 W和R263 Q多态性的次要等位基因的总体效应。在西班牙队列中，PTPN 22 263 Q功能丧失变体显示与UC相关的初步证据（P =0.026，比值比[OR] = 0.61，95%置信区间[CI]：0.39-0.95），这在荟萃分析中得到证实（P = 0.013汇总，OR 0.69，95% CI：0.51-0.93）。与此相反，263 Q等位基因显示与CD无关（P = 0.22汇总，OR = 1.16，95%CI：0.91-1.47）。我们在汇总分析中发现，PTPN 22 620 W功能获得性变体与CD风险降低相关（P = 7.4E-06合并OR 0.81，95% CI：0.75-0.89），但不是UC结论：PTPN 22基因的两个自身免疫相关的多态性与CD和UC的发病有差异。R263 Q多态性仅与UC相关，而R620 W多态性仅与CD显著相关。（炎症性肠病2011;17：2287-2294）
Background: The PTPN22 gene is an important risk factor for human autoimmunity. The aim of this study was to evaluate for the first time the role of the R263Q PTPN22 polymorphism in ulcerative colitis (UC) and Crohn's disease (CD), and to reevaluate the association of the R620W PTPN22 polymorphism with both diseases.Methods: A total of 1677 UC patients, 1903 CD patients, and 3111 healthy controls from an initial case-control set of Spanish Caucasian ancestry and two independent sample sets of European ancestry (Dutch and New Zealand) were included in the study. Genotyping was performed using TaqMan SNP assays for the R263Q (rs33996649) and R620W (rs2476601) PTPN22 polymorphisms. Meta-analysis was performed on 6977 CD patients, 5695 UC patients, and 9254 controls to test the overall effect of the minor allele of R620W and R263Q polymorphisms.Results: The PTPN22 263Q loss-of-function variant showed initial evidence of association with UC in the Spanish cohort (P =0.026, odds ratio [OR] = 0.61, 95% confidence interval [CI]: 0.39-0.95), which was confirmed in the meta-analysis (P = 0.013 pooled, OR 0.69, 95% CI: 0.51-0.93). In contrast, the 263Q allele showed no association with CD (P = 0.22 pooled, OR = 1.16, 95% CI: 0.91-1.47). We found in the pooled analysis that the PTPN22 620W gain-of-function variant was associated with reduced risk of CD (P = 7.4E-06 pooled OR 0.81, 95% CI: 0.75-0.89) but not of UC (P = 0.88 pooled, OR = 0.98, 95% CI: 0.85-1.15).Conclusions: Our data suggest that two autoimmunity-associated polymorphisms of the PTPN22 gene are differentially associated with CD and UC. The R263Q polymorphism only associated with UC, whereas the R620W was significantly associated with only CD. (Inflamm Bowel Dis 2011;17:2287-2294)