title: Association studies of TNFSF4, TNFAIP3 and FAM167A-BLK polymorphisms with primary Sjogren's syndrome in Han Chinese.
abstract: Single-nucleotide polymorphisms (SNPs) in the TNFSF4, TNFAIP3 and FAM167A-BLK genes have been associated with several autoimmune diseases. Associations of TNFSF4 and FAM167A-BLK with primary Sjogren's syndrome (pSS) have also been described in a Caucasian population. However, it remains unknown whether polymorphisms of TNFSF4, TNFAIP3 and FAM167A-BLK are associated with pSS in Han Chinese. This study aimed to determine whether SNPs in TNFSF4, TNFAIP3 or FAM167A-BLK genetically predispose a Chinese Han population to pSS. Ten SNPs in the TNFSF4 region (rs1234315, rs2205960, rs844648 and rs704840), the TNFAIP3 gene (rs5029939 and rs2230926) and the FAM167A-BLK region (rs7812879, rs2254546, rs2618479 and rs2248932) were genotyped in a cohort of 555 pSS patients and 597 healthy controls, by using the Sequenom MassArray system. Weak associations were observed when the SNPs in TNFSF4 (rs2205960, rs844648 and rs704840) and FAM167A-BLK (rs7812879, rs2254546 and rs2618479) were directly analyzed or analyzed under dominant model between pSS and controls (all P<0.05). However, when Bonferroni correction was applied to the multiple comparisons, all of the associations vanished, except for rs7812879 (Pa=0.045). The frequencies of alleles, genotypes and haplotypes of TNFAIP3 SNPs and rs2248932 of FAM167A-BLK were not significantly different between the pSS patients and controls. No epistatic interactions were found to exist between the SNPs examined. Unlike the SNPs in TNFAIP3 and TNFSF4, rs7812879 in FAM167A-BLK imparts susceptibility to pSS in a Han Chinese population. The differential genetic risk profiles from other autoimmune diseases may indicate differential molecular mechanisms underlying pSS pathogenesis in this group.
authors: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
authors: Fei
authors: F
authors: Sun
authors: Ping
authors: P
authors: Li
authors: Hua
authors: H
authors: Chen
authors: Ziyan
authors: Z
authors: Wu
authors: Juanjuan
authors: J
authors: Xu
authors: Min
authors: M
authors: Shen
authors: Xiaomei
authors: X
authors: Leng
authors: Qun
authors: Q
authors: Shi
authors: Wen
authors: W
authors: Zhang
authors: Xinping
authors: X
authors: Tian
authors: Yongzhe
authors: Y
authors: Li
authors: Fengchun
authors: F
authors: Zhang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D053278:OX40 Ligand / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D064267:Intrinsically Disordered Proteins
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D053278:OX40 Ligand; D011506:Proteins; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C584607:FAM167A protein, human; D064267:Intrinsically Disordered Proteins; C089251:TNFSF4 protein, human; C076529:TNFAIP3 protein, human