Brief Report: High‐Throughput Sequencing of IL23R Reveals a Low‐Frequency, Nonsynonymous Single‐Nucleotide Polymorphism That Is Associated With Ankylosing Spondylitis in a Han Chinese Population. Issue 7 (2nd July 2013)

• Record Type: Journal Article
• Authors: Davidson, Stuart I.; Jiang, Lei; Cortes, Adrian; Wu, Xin; Glazov, Evgeny A.; Zheng, Yi; Danoy, Patrick A.; Liu, Yi; Thomas, Gethin P.; Brown, Matthew A.; Xu, Huji
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 7(2013:Jul.)
• Page Start: 1747
• Page End: 1752
• Publication Date: 2013-07-02
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.37976
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art37976-sec-0001" sec-type="section"> <title>Objective</title> <p>Ankylosing spondylitis (AS) is a highly heritable common inflammatory arthritis that targets the spine and sacroiliac joints of the pelvis, causing pain and stiffness and leading eventually to joint fusion. Although previous studies have shown a strong association of <italic>IL23R</italic> with AS in white Europeans, similar studies in East Asian populations have shown no association with common variants of <italic>IL23R</italic>, suggesting either that <italic>IL23R</italic> variants have no role or that rare genetic variants contribute. The present study was undertaken to screen <italic>IL23R</italic> to identify rare variants associated with AS in Han Chinese.</p> </sec> <sec id="art37976-sec-0002" sec-type="section"> <title>Methods</title> <p>A 170‐kb region containing <italic>IL23R</italic> and its flanking regions was sequenced in 50 patients with AS and 50 ethnically matched healthy control subjects from a Han Chinese population. In addition, the 30‐kb region of peak association in white Europeans was sequenced in 650 patients with AS and 1, 300 healthy controls. Validation genotyping was undertaken in 846 patients with AS and 1, 308 healthy controls.</p> </sec> <sec id="art37976-sec-0003" sec-type="section"> <title>Results</title> <p>We identified 1, 047 variants, of which 729 were not found in the dbSNP genomic build 130. Several potentially functional rare variants in <italic>IL23R</italic> were identified, including one nonsynonomous single‐nucleotide polymorphism (nsSNP), Gly<sup>149</sup>Arg (position 67421184 GA on chromosome 1). Validation genotyping showed that the Gly<sup>149</sup>Arg variant was associated with AS (odds ratio 0.61, <italic>P</italic> = 0.0054).</p> </sec> <sec id="art37976-sec-0004" sec-type="section"> <title>Conclusion</title> <p>This is the first study to implicate rare <italic>IL23R</italic> variants in the pathogenesis of AS. The results identified a low‐frequency nsSNP with predicted loss‐of‐function effects that was protectively associated with AS in Han Chinese, suggesting that decreased function of the interleukin‐23 (IL‐23) receptor protects against AS. These findings further support the notion that IL‐23 signaling has an important role in the pathogenesis of AS.</p> </sec> </abstract>