锌指蛋白基因IKZF3多态性与中国长江以南汉族人群系统性红斑狼疮的病例对照研究

目的 研究IKZF3基因多态性与中国长江以南汉族人群系统性红斑狼疮（SLE）易感性间的关联性。方法 采用病例对照研究（SLE 213例，正常健康对照者234例），应用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）方法检测IKZF3基因多态性。在多个遗传模型（加性、隐性、显性）下，利用多因素logistic回归模型和广义多因子降维模型（GMDR），分析基因与疾病易感性、疾病临床表型之间的关系，以及基因-基因交互作用，并进行生物信息学分析。结果 IKZF3基因rs114509391位点CA基因型的个体较AA基因型的个体患SLE的风险下降（OR=0.14，95%CI：0.03～0.56，P=0.006）；且在显性模型仍存在统计学意义（OR=0.26，95%CI：0.09～0.81，P=0.02）。分层分析提示rs9635726和rs9909593两位点可能与SLE发病也存在关联。表型研究显示，rs907091位点与肾脏损害（加性模型：OR=0.59，95%CI：0.35～0.98，P=0.043）、抗SSB抗体阳性（显性模型：OR=0.41，95%CI：0.18～0.96，P=0.040）相关；rs9909593位点GG、GA基因型的患者出现抗SSB抗体阳性的风险也较AA基因型患者下降（OR=0.37，95%CI：0.16～0.88，P=0.025）。生物信息学分析提示研究位点为功能位点。结论 IKZF3基因rs114509391、rs9635726和rs9909593可能与SLE易感性相关，rs9909593、rs907091与SLE的临床表型相关。

Association between IKZF3 gene polymorphisms and systemic lupus erythematosus in Han ethnic group in southern China: a case-control study

Objective To understand the association between IKZF3 gene polymorphism and the risk of systemic lupus erythematosus (SLE) in Han ethnic group in southern China. Methods A case-control study was conducted among 213 SLE patients and 234 healthy controls. Venous blood samples were collected from them to measure single nucleotide polymorphism (SNP) in IKZF3 by using the method of restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic analysis and generalized multifactor dimensionality reduction (GMDR) method were used under multiple genetic models (additive, dominant, recessive), to analyze the association between IKZF3 and SLE susceptibility or different clinical features and gene-gene interactions. In addition, bioinformatics analysis was also conducted. Results As for rs114509391, CA genotype might decrease the risk of SLE compared with AA genotype (OR=0.14, 95%CI:0.03-0.56, P=0.006) and significant association was also observed under dominant model (OR=0.26, 95%CI:0.09-0.81, P=0.02). Stratified analysis indicated that rs9635726 and rs9909593 were related to SLE onset. The study of clinical features showed that rs907091 was associated with both renal disorder (additive:OR=0.59, 95%CI:0.35-0.98, P=0.043) and anti-SSB (dominant:OR=0.41, 95%CI:0.18-0.96, P=0.040). rs9635726 GG and GA genotype might decrease the risk of anti-SSB compared with AA genotype (OR=0.37, 95%CI:0.16-0.88, P=0.025). In addition, bioinformatics analysis indicated that all the studied SNPs were functional. Conclusion IKZF3 rs114509391, rs9635726 and rs9909593 polymorphisms might be related to SLE susceptibility in Han ethnic group in southern China and rs9909593, rs907091 might be associated with renal disorder and anti-SSB.