FAM167A—BLK和TNFSF4基因多态性与原发性干燥综合征的遗传相关性  

Association studies of FAM167A-BLK and TNFSF4 polymorphisms with primary Sjogren＇ s syndrome

作　　者：孙菲[1] 李萍[1] 吴子燕[1] 徐涓娟[1] 陈华[1] 田新平[1] 张奉春[1] 李永哲[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院风湿免疫科风湿免疫病学教育部重点实验室,100032

出　　处：《中华检验医学杂志》2013年第8期693-698,共6页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金资助项目（81072486、81172857）;国家十一五科技支撑计划资助项目（2008BA159803）;卫生公益性行业科研专项（201202004）

摘　　要：目的探讨中国汉族人群中与其他自身免疫性疾病相关的FAM167A—BLK和TNFSF4基因区域多态性是否与原发性干燥综合征（pSS）存在遗传相关性。方法临床对照研究。选取2008年11月至2011年12月北京协和医院515例中国汉族pSS患者和567名健康体检者，对所有候选单核苷酸多态性（SNP）位点采用时间飞行质谱生物芯片系统（Sequenom MassArray）进行基因分型。采用X^2检验、logistic回归分析对SNP位点的基因型、等位基因、上位效应和单体型进行相关性分析，并在3种遗传模型（加性、显性和隐性）下对各SNP位点进行相关性分析。结果FAM167A—BLK基因区域的rs7812879和rs2254546位点在pSS组的基因型频率为：TT6．2％，TC28．5％，CC65．2％；AA6．0％，AG30．0％，GG64．0％；在健康对照组的基因型频率为：TT4．7％，TC38．2％，CC57．1％；AA5．1％，AG39．3％，GG55．6％，差异有统计学意义（X^2=11．09、9．91，Pa〈0．05）。且在显性遗传模型下，rs7812879（OR=0．71，Pa=0．044）、rs2254546（OR=0．70，Pa=0．037）和rs2736340（OR=0．71，Pn=0．039）3个SNP位点基因型分布在pSS组和健康对照组之间差异均有统计学意义。rs7812879、rs2254546和rs2736340位点组成的CGT单体型在pSS组和健康对照组的频率分别为75．7％和70．8％，差异有统计学意义（X^2=6．36，P=0．012）。在各种分析中未发现FAM167A—BLK基因区域的rs2248932和TNFSF4（rs2205960和rs704840）基因多态性与pSS相关（P均〉0．05），且FAM167A—BLK和TNFSF4基因区域内未发现所选SNP位点存在上位效应（P均〉0．05）。结论在汉族人群中FAM167A—BLK基因区域的rs7812879、rs2254546和rs2736340位点与pSS的遗传易感性密切相关，而FAM167A—BLK基因区域的rs2248932以及TNFSF4基因区域的rs2205960和rs704840与pSS的易感性无明确相关性。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 MassArray 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 Genotypc 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 （ X^2 = 11.09, Pa = 0. 023 ; X^2 = 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 = O. 71, Pa = 0. 044; OR = 0. 70,Pa = 0. 037; OR = O. 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 （ X2 = 6. 36, P = 0. 012 ）. The frequencies of alleles and genotypes of rs2248932 in FAM167A-BLK and TNFSF4 SNPs were not significantly different between the pSS patients and controls （ all Pa 〉 0. 05 ）. No epistatic interaetions were found to exist between the SNPs examined. Conclusions Our results indieated that FAM167A-BLK SNPs （rs

关 键 词：干燥综合征 多态性 单核苷酸 蛋白酪氨酸激酶类 

分 类 号：R593.2[医药卫生—内科学]