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多个与先天和适应性免疫反应都有关的位点的变异与干燥综合征有关。

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome.

机构信息

1] Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. [2] Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

出版信息

Nat Genet. 2013 Nov;45(11):1284-92. doi: 10.1038/ng.2792. Epub 2013 Oct 6.

DOI:10.1038/ng.2792
PMID:24097067
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3867192/
Abstract

Sjögren's syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10(-19)), STAT4 (Pmeta = 6.80 × 10(-15)), IL12A (Pmeta = 1.17 × 10(-10)), FAM167A-BLK (Pmeta = 4.97 × 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 × 10(-8)) and TNIP1 (Pmeta = 3.30 × 10(-8)). We also observed suggestive associations (Pmeta < 5 × 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögren's syndrome.

摘要

干燥综合征是一种常见的自身免疫性疾病（影响约 0.7%的欧洲裔美国人），通常表现为干燥性角膜结膜炎和口干。在这里，我们报告了干燥综合征的一项大规模关联研究结果。除了在 6p21 上人类白细胞抗原（HLA）区域内的强烈关联（Pmeta = 7.65 × 10(-114)）之外，我们还与 IRF5-TNPO3（Pmeta = 2.73 × 10(-19)）、STAT4（Pmeta = 6.80 × 10(-15)）、IL12A（Pmeta = 1.17 × 10(-10)）、FAM167A-BLK（Pmeta = 4.97 × 10(-10)）、DDX6-CXCR5（Pmeta = 1.10 × 10(-8)）和 TNIP1（Pmeta = 3.30 × 10(-8)）建立了关联。我们还观察到 29 个其他区域的变异与干燥综合征存在提示性关联（Pmeta < 5 × 10(-5)），包括 TNFAIP3、PTTG1、PRDM1、DGKQ、FCGR2A、IRAK1BP1、ITSN2 和 PHIP 等。这些结果突出了参与固有和适应性免疫的基因在干燥综合征中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70d4/3867192/45dcd8dfcdea/emss-54762-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70d4/3867192/133cdedcb6ee/emss-54762-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70d4/3867192/169332a7c1ba/emss-54762-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70d4/3867192/45dcd8dfcdea/emss-54762-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70d4/3867192/133cdedcb6ee/emss-54762-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70d4/3867192/169332a7c1ba/emss-54762-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70d4/3867192/45dcd8dfcdea/emss-54762-f0003.jpg

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