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PLoS By Category | Recent PLoS Articles
Rheumatology

Association of ORAI1 Haplotypes with the Risk of HLA-B27 Positive Ankylosing Spondylitis
Published: Wednesday, June 01, 2011
Author: James Cheng-Chung Wei et al.

by James Cheng-Chung Wei, Jeng-Hsien Yen, Suh-Hang Hank Juo, Wei-Chiao Chen, Yu-Shiuan Wang, Yi-Ching Chiu, Tusty-Jiuan Hsieh, Yuh-Cherng Guo, Chun-Huang Huang, Ruey-Hong Wong, Hui-Po Wang, Ke-Li Tsai, Yang-Chang Wu, Hsueh-Wei Chang, Edward Hsi, Wei-Pin Chang, Wei-Chiao Chang

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.
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