title: Association of ORAI1 haplotypes with the risk of HLA-B27 positive ankylosing spondylitis.
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.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chung Shan Medical University Hospital, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: James Cheng-Chung
authors.initials: JC
authors.lastname: Wei
authors.forename: Jeng-Hsien
authors.initials: JH
authors.lastname: Yen
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chen
authors.forename: Yu-Shiuan
authors.initials: YS
authors.lastname: Wang
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chiu
authors.forename: Tusty-Jiuan
authors.initials: TJ
authors.lastname: Hsieh
authors.forename: Yuh-Cherng
authors.initials: YC
authors.lastname: Guo
authors.forename: Chun-Huang
authors.initials: CH
authors.lastname: Huang
authors.forename: Ruey-Hong
authors.initials: RH
authors.lastname: Wong
authors.forename: Hui-Po
authors.initials: HP
authors.lastname: Wang
authors.forename: Ke-Li
authors.initials: KL
authors.lastname: Tsai
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
authors.forename: Edward
authors.initials: E
authors.lastname: Hsi
authors.forename: Wei-Pin
authors.initials: WP
authors.lastname: Chang
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015220:Calcium Channels / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071740:ORAI1 Protein; D011110:Polymorphism, Genetic; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D015220:Calcium Channels; D015796:HLA-B27 Antigen; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human