Abstract
Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The aetiology of ankylosing spondylitis is still unclear. Previous studies have indicated that genetics factors such as human leukocyte antigen HLA-B27 associates to AS susceptibility. We carried out a case-control study to determine whether the genetic polymorphisms of ORAI1 gene, a major component of store-operated calcium channels that involved the regulation of immune system, is a susceptibility factor to AS in a Taiwanese population. We enrolled 361 AS patients fulfilled the modified New York criteria and 379 controls from community. Five tagging single nucleotides polymorphisms (tSNPs) at ORAI1 were selected from the data of Han Chinese population in HapMap project. Clinical statuses of AS were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Index (BAS-G). Our results indicated that subjects carrying the minor allele homozygote (CC) of the promoter SNP rs12313273 or TT homozygote of the SNP rs7135617 had an increased risk of HLA-B27 positive AS. The minor allele C of 3′UTR SNP rs712853 exerted a protective effect to HLA-B27 positive AS. Furthermore, the rs12313273/rs7135617 pairwise allele analysis found that C-G (OR 1.69, 95% CI 1.27, 2.25; p = 0.0003) and T-T (OR 1.75, 95% CI 1.36, 2.27; p<0.0001) haplotypes had a significantly association with the risk of HLA-B27-positive AS in comparison with the T-G carriers. This is the first study that indicate haplotypes of ORAI1 (rs12313273 and rs7135617) are associated with the risk of HLA-B27 positive AS.
Highlights
Ankylosing spondylitis (AS) is a systemic autoimmune disease affecting axial skeletons and peripheral joints[1]
Two polymorphisms of ORAI1 located in the promoter area, while two polymorphisms in the intron and one in the 39 untranslated region (UTR)
Our results first revealed that genetic polymorphisms of ORAI1 rs12313273, rs7135617 and rs712853 were associated with susceptibility to AS in a Taiwanese population
Summary
Ankylosing spondylitis (AS) is a systemic autoimmune disease affecting axial skeletons and peripheral joints[1]. Genetic factors have been strongly implicated in its pathogenesis. A twin study suggested that up to 97% of AS susceptibility was attributable to genetic factors[3]. AS was strongly associated with the human leukocyte antigen HLAB27 gene[4], but HLA-B27 accounted for only 16% of the genetic load in AS[5]. A recent genome wide association study (GWAS) demonstrated immune related genes such as ERAP1, and IL-23 as strong susceptibility genes to AS[9]. In the Chinese Han population, Janus kinase 2 (JAK2) polymorphisms have been implicated to be involved in the susceptibility of AS[13]. Several genes have been proposed to explain the susceptibility of AS, most genetic associations study cannot be replicated with other populations
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