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鉴定 PTPN22 功能变体 R620W 为巨细胞动脉炎的易感性遗传因素。

Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis.

机构信息

Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.

NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, West Yorkshire, UK.

出版信息

Ann Rheum Dis. 2013 Nov;72(11):1882-1886. doi: 10.1136/annrheumdis-2013-203641. Epub 2013 Aug 14.

DOI:
10.1136/annrheumdis-2013-203641
PMID:23946333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4053592/
Abstract

OBJECTIVE

To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA).

METHODS

Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays.

RESULTS

The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79).

CONCLUSIONS

Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

摘要

目的

分析先前与自身免疫相关的 PTPN22 和 CSK 基因在巨细胞动脉炎（GCA）易感性和临床表型中的作用。

方法

我们的研究人群由来自西班牙发现队列的 911 名经活检证实的 GCA 患者和 8136 名无 GCA 对照组成，并由来自德国、挪威和英国的三个额外独立复制队列进行补充。使用预设计的 TaqMan 检测方法对两个功能性 PTPN22 多态性（rs2476601/R620W 和 rs33996649/R263Q）和 CSK 基因的两个变体（rs1378942 和 rs34933034）进行基因分型。

结果

发现队列的分析提供了 PTPN22 rs2476601/R620W 与 GCA 相关的证据（PFDR=1.06E-04，OR=1.62，95%CI 1.29 至 2.04）。该关联似乎不符合特定的 GCA 亚表型。在病例/对照或分层病例分析中，其他 PTPN22 和 CSK 遗传变异的等位基因频率之间也没有明显的统计学差异。为了确认检测到的 PTPN22 关联，对三个复制队列进行了基因分型，总体荟萃分析显示 PTPN22 rs2476601/R620W 变异与 GCA 之间存在一致的关联（PMH=2.00E-06，OR=1.51，95%CI 1.28 至 1.79）。

结论

我们的结果表明，PTPN22 多态性 rs2476601/R620W 在外周动脉疾病的遗传风险中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d48/4053592/ab9b8b4fbe90/emss-58672-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d48/4053592/ab9b8b4fbe90/emss-58672-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d48/4053592/ab9b8b4fbe90/emss-58672-f0001.jpg

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