IkB激酶β和DNA聚合酶β易感基因位点与中国汉族人群系统性红斑狼疮的相关性研究

摘要

目的 分析IkB激酶β(IKBKB)rs12676482,rs2272733和DNA聚合酶β(POLB)rs3136717,rs3136744基因单核苷酸多态性(SNPs)与中国汉族人群SLE遗传易感性的关系,探讨这些位点与SLE的相关性.方法 采用PCR-连接酶检测反应(LDR)技术对908例SLE患者和961名健康对照进行基因分型,结合SLE实验室及临床表现,分析该位点与疾病及临床表型的相关性.分型结果用PLINK1.07软件进行统计分析,所选SNP位点等位基因频率和基因型频率进行x2检验,3种遗传模型(加性模型、显性模型和隐性模型)基因型频率应用Logistic回归进行分析.结果 rs12676482在对照组中AA、AG、GG基因型频率和A、G等位基因频率分别为0.9％(8/938)、15.7％(147/938)、83.4％ (783/938)、8.7％(163/1 876)、91.3％(1 713/1 876),SLE组中为1.4％(12/888)、15.6％(139/888)、83.0％ (737/888)、9.2％(163/1 776)、90.2％(1613/1 776),2组基因型频率和等位基因频率差异均无统计学意义(P＞0.05);rs2272733在对照组中TT、TC、CC基因型频率和T、C等位基因频率分别为1.1％(10/938)、16.7％(157/938)、82.2％(771/938)、9.4％(177/1 876)、90.6％(1 699/1 876),SLE组中为1.4％(12/888)、16.3％(145/888)、82.3％(731/888)、9.5％(169/1 776)、90.5％(1 607/1 776),2组基因型频率和等位基因频率差异均无统计学意义(P＞0.05);rs3136717在对照组中CC、CT、TT基因型频率和C、T等位基因频率分别为1.1％(10/938)、16.7％(157/938)、82.2％(771/938)、9.4％(177/1 876)、90.6％(1 699/1 876),SLE组中为1.4％(12/888)、16.7％(148/888)、82.0％(728/888)、9.7％(172/1 776)、90.3％(1 604/1 776),2组基因型频率和等位基因频率差异均无统计学意义(P＞0.05);rs3136744在对照组中CC、CA、AA基因型频率和C、A等位基因频率分别为0.6％(6/938)、13.6％(128/938)、85.7％(804/938)、7.4％(140/1 876)、92.6％(1 736/1 876),SLE组中为1.0％(9/888)、14.4％(128/888)、84.6％ (751/888)、8.2％(146/1 776)、91.8％(1 630/1 776),2组基因型频率和等位基因频率差异均无统计学意义(P＞0.05).加性模型、显性模型及隐性模型下分析显示2组间差异均无统计学意义(P＞0.05).将SLE患者按血清学指标及临床表现分型,评估疾病活动度,未发现上述位点与临床指标之间相关(P＞0.05).结论 rs12676482,rs2272733(IKBKB)和rs3136717,rs3136744(POLB)位点多态性与中国汉族人群SLE易感性不相关.%Objective To investigate the association of single nucleotide polymorphisms (SNPs) of IKBKB (rs 12676482,rs2272733) and POLB (rs3136717,rs3136744)with systemic lupus erythematosus (SLE)in Chinese Han population.Methods SNPs from a cohort of 908 SLE patients and 961 healthy controls were genotyped using polymerase chain reaction-ligase detection reaction (PCR-LDR).The associations of the SNPs with the clinical manifestations and various serological markers of SLE were analyzed.x2-test was applied to compare allele and genotype frequencies between cases and controls using the PLINK 1.07 software.Three Logistic regression models (additive,dominant,and recessive) were used to analyze the SNPs.Results In the healthy control group,rs12676482 AA,AG,GG genotype frequency and A,G allele frequencies were as follows:0.9％ (8/938),15.7％ (147/938),83.4％ (783/938),8.7％ (163/1 876),91.3％ (1 713/1 876),those of the corresponding case group were as follows:1.4％(12/888),15.6％(139/888),83.0％(737/888),9.2％(163/1 776),90.2％(1 613/1 776),genotype and allele frequencies were not statistical significantly different between SLE patients and healthy controls (P＞0.05).In healthy control group,rs2272733 TT,TC,CC genotype frequency and T,C allele frequencies were as follows:1.1％(10/938),16.7％(157/938),82.2％(771/938),9.4％(177/1 876),90.6％(1 699/1 876),those of the SLE patients group was as follows:1.4％(12/888),16.3％(145/888),82.3％(731/888),9.5％(169/1 776),90.5％(1 607/1 776),genotype and allele frequencies were not statistical significantly different between SLE patients and healthy controls (P ＞0.05).In the healthy control group,rs3136717 CC,CT,TT genotype frequency and C,T allele frequencies were as follows:1.1％(10/938),16.7％(157/938),82.2％(771/938),9.4％(177/1 876),90.6％(1 699/1 876),those of the patient group were as follows:1.4％ (12/888),16.7％ (148/888),82.0％ (728/888),9.7％ (172/1 776),90.3％ (1 604/1 776),genotype and allele frequencies were not statistic ally significantly different between SLE patients and healthy controls (P＞0.05).In the healthy control group,rs3136744 CC,CA,AA genotype frequency and C,A allele frequencies were as f ollows:0.6％(6/938),13.6％(128/938),85.7％(804/938),7.4％(140/1 876),92.6％(1 736/1 876),those of the patients group were as follows:1.0％(9/888),14.4％(128/888),84.6％(751/888),8.2％(146/1 776),91.8％ (1 630/1 776),genotype and allele frequencies were not statistically significantly difference between SLE patients and healthy controls (P＞0.05).The genotype frequencies were not different between the three genetic models.There was no evidence of association between the two SNPs and any clinical features of SLE (P＞0.05).Conclusion rs12676482,rs2272733(IKBKB) and rs3136717,rs3136744(POLB) are not susceptible genes for SLE in Chinese Han population.