High-throughput sequencing of IL23R reveals a low-frequency, nonsynonymous single-nucleotide polymorphism that is associated with ankylosing spondylitis in a Han Chinese population

Davidson, S. I., Jiang, L., Cortes, A., Wu, X., Glazov, E. A., Zheng, Y., Danoy, P. A., Liu, Y., Thomas, G. P., Brown, Matthew A., & Xu, H. (2013) High-throughput sequencing of IL23R reveals a low-frequency, nonsynonymous single-nucleotide polymorphism that is associated with ankylosing spondylitis in a Han Chinese population. Arthritis and Rheumatism, 65(7), pp. 1747-1752.

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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 IL23R with AS in white Europeans, similar studies in East Asian populations have shown no association with common variants of IL23R, suggesting either that IL23R variants have no role or that rare genetic variants contribute. The present study was undertaken to screen IL23R to identify rare variants associated with AS in Han Chinese.


A 170-kb region containing IL23R 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.


We identified 1,047 variants, of which 729 were not found in the dbSNP genomic build 130. Several potentially functional rare variants in IL23R were identified, including one nonsynonomous single-nucleotide polymorphism (nsSNP), Gly149Arg (position 67421184 GA on chromosome 1). Validation genotyping showed that the Gly149Arg variant was associated with AS (odds ratio 0.61, P = 0.0054).


This is the first study to implicate rare IL23R 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.

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ID Code: 87772
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: arginine, interleukin 23 receptor, messenger RNA, IL23R protein, human, interleukin receptor, allele, ankylosing spondylitis, article, Chinese, chromosome 1, clinical article, controlled study, disease association, DNA flanking region, gene frequency, genetic association, genetic transcription, genetic variability, genomics, genotype, high throughput sequencing, human, priority journal, single nucleotide polymorphism, Asian, case control study, China, ethnology, genetic predisposition, genetics, Asian Continental Ancestry Group, Case-Control Studies, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Receptors, Interleukin, Spondylitis, Ankylosing
DOI: 10.1002/art.37976
ISSN: 0004-3591
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 28 Sep 2015 06:11
Last Modified: 22 Feb 2016 05:08

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