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.
J Hum Genet. 2013 Jul;58(7):475-9. doi: 10.1038/jhg.2013.26. Epub 2013 May 2.
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.
单核苷酸多态性（SNPs）在 TNFSF4、TNFAIP3 和 FAM167A-BLK 基因中与多种自身免疫性疾病有关。在高加索人群中，TNFSF4 和 FAM167A-BLK 与原发性干燥综合征（pSS）之间也存在关联。然而，在汉族人群中，TNFSF4、TNFAIP3 和 FAM167A-BLK 的多态性是否与 pSS 相关仍不清楚。本研究旨在确定 TNFSF4、TNFAIP3 或 FAM167A-BLK 的 SNP 是否使汉族人群易患 pSS。在一个由 555 例 pSS 患者和 597 名健康对照组成的队列中，使用 Sequenom MassArray 系统对 TNFSF4 区域（rs1234315、rs2205960、rs844648 和 rs704840）、TNFAIP3 基因（rs5029939 和 rs2230926）和 FAM167A-BLK 区域（rs7812879、rs2254546、rs2618479 和 rs2248932）中的 10 个 SNP 进行了基因分型。当直接分析 pSS 与对照组之间的 TNFSF4（rs2205960、rs844648 和 rs704840）和 FAM167A-BLK（rs7812879、rs2254546 和 rs2618479）中的 SNP 或在显性模型下进行分析时，观察到与 SNPs 较弱的关联（均 P<0.05）。然而，当对多重比较进行 Bonferroni 校正时，除 rs7812879（Pa=0.045）外，所有关联均消失。TNFAIP3 SNP 的等位基因、基因型和单体型频率以及 FAM167A-BLK 的 rs2248932 在 pSS 患者和对照组之间无显著差异。未发现所检查的 SNP 之间存在上位性相互作用。与 TNFAIP3 和 TNFSF4 中的 SNP 不同，FAM167A-BLK 中的 rs7812879 赋予汉族人群 pSS 的易感性。与其他自身免疫性疾病的 SNP 不同，这可能表明 pSS 发病机制在该人群中存在不同的分子机制。
