Association studies of FAM167A-BLK and TNFSF4 polymorphisms with primary Sjögren′s syndrome

Objective To investigate whether single nucleotide polymorphisms (SNPs) in the FAM167A-BLK (rs7812879,rs2254546,rs2736340 and rs2248932) and TNFSF4 (rs2205960 and rs704840) region which have been associated with other autoimmune diseases could be associated with pSS in Chinese Han. Methods This study was designed as a case-control.The SNPs were genotyped in a cohort of 515 primary Sjogren′s syndrome (pSS) patients and 567 healthy controls,by using the Sequenom Mass Array system.The genotypes,alleles,epistasis and haplotypes of the SNPs were analyzed with PLINK1.07 and Haploview v4.2 using chi-square test,logistic regression analysis and Bonferroni correction,SNPs were further analyzed under three genetic models (additive,dominant,and recessive). Results Genotype distribution of rs7812879 and rs2254546 in pSS patients were as follows: TT 6.2%,TC 28.5%,CC 65.2%; AA 6.0%,AG 30.0%,GG 64.0% respectively,correspondingly in healthy controls were as follows: TT 4.7%,TC 38.2%,CC 57.1%;AA 5.1%,AG 39.3%,GG 55.6%,and significant differences were observed between pSS patients and controls (χ2=11.09,Pa=0.023;χ2=9.91,Pa=0.042 respectively).Genotype distribution of the three SNPs (rs7812879,rs2254546,rs2736340) were all significant different between pSS patients and controls under the dominant genetic model (OR=0.71,Pa=0.044; OR=0.70,Pa=0.037; OR=0.71,Pa=0.039 respectively).The frequencies of haplotype CGT formed by rs7812879,rs2254546 and rs2736340 in pSS patients and healthy controls were 75.7% and 70.8%,respectively.So haplotype CGT was strongly associated with pSS (χ2=6.36,P=0.012).The frequencies of alleles and genotypes of rs2248932 in FAM167 A-BLK and TNFSF4 SNPs were not significantly different between the pSS patients and controls (all Pa>0.05).No epistatic interactions were found to exist between the SNPs examined. Conclusions Our results indicated that FAM167A-BLK SNPs (rs7812879,rs2254546,rs2736340) imparts susceptibility to pSS in Han Chinese,but not rs2248932 in FAM167A-BLK or the TNFSF4 SNPs (rs2205960 and rs704840).(Chin J Lab Med,2013,36:693-698) Key words: Sjogren′s syndrome; Polymorphism; single nucleotide; Proterin-tyrosine kinases