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

Abstract

Objective. 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. Conclusion. 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.

Progress of genome‐wide association studies of ankylosing spondylitis

“…Rather, a different variant (rs76418789, G149R) is AS-associated in east Asians. 55 This variant shows weak association in European descent populations too but that effect is difficult to see because of the strength of association of other variants at this locus, notably rs11209026 (R381Q).…”

The immunogenetics of Behçet's disease: A comprehensive review

“…These two SNPs are in moderate LD (r 2 = 0.63, Table 2) and may detect the same functional variant in both populations. Interestingly, low frequency missense variants of the IL23R (p.Arg381Gln in the Turkish population and p.Gly149Arg in the Japanese population) that reduce its ability to respond to IL-23 stimulation have been associated with protection from BD [69], as well as from ankylosing spondylitis (AS) [70, 71], psoriasis [72, 73], Crohn’s disease [74], ulcerative colitis [75] and inflammatory bowel disease (IBD) [76, 77], suggesting that the intergenic disease-associated common non-coding variants might be associated with increased expression of IL23R compared with the disease-protective minor alleles.…”

Review: The Interleukin‐23/Interleukin‐17 Axis in Spondyloarthritis Pathogenesis: Th17 and Beyond

“…While the association was confirmed in subsequent studies of individuals of European descent (13), the IL23R association was not found in Korean (48) or Chinese populations (41,49). However, a recent study identified several rare IL23R variants in a Chinese population, including a non-synonymous SNP predicted to reduce function that is associated with protection from AS (50). …”