免疫球蛋白受体ⅡB和ⅢA基因多态性与新疆维吾尔族SLE的遗传易感性分析

Association of Polymorphisms in Immunoglobulin Receptor ⅡB and ⅢA Genes with Hereditary Susceptibility of Systemic Lupus Erythematosus in Xinjiang

目的观察分析免疫球蛋白受体(FCγR)ⅡB和ⅢA基因多态性与新疆维吾尔族系统性红斑狼疮(SLE)的遗传易感性。方法人类1号染色体长臂2区3带(1q23) FCγRⅡB和ⅢA基因多态性通过应用聚合酶链反应和限制性酶切片段长度多态性方法进行测定,同时以问卷调查方式收集103个新疆维吾尔族家系(其中包括87个新疆维吾尔族SLE核心家系)的一般流行病学资料和DNA血样,采用家系内关联性分析(FBAT)对所选SLE核心家系的FCγRⅡB和ⅢA基因中13个功能单核苷酸多态性位点进行等位基因和基因型分析。结果单位点的家系关联性分析结果显示:在FCγRⅡB基因中,只有rs10917661、rs1050501两个单核苷酸多态性位点是SLE遗传的重要易感位点;在FCγRⅢA基因中,只有rs403016、rs28888两个单核苷酸多态性位点是SLE遗传的重要易感位点。单倍型分析结果显示:在FcγRⅡB基因中,只有50Ter-225Thr单倍型与SLE遗传易感性有关;在FcγRⅢA基因中,只有72Arg-118Asn单倍型与SLE的遗传易感性有关;在FCγRⅡB和ⅢA基因中,未发现与SLE存在遗传易感性的单倍型,提示FcγRⅡB和FcγRⅢA基因在SLE的遗传易感性中可能对立发挥作用。结论 FcγRⅡB和FcγRⅢA基因存在与新疆维吾尔族SLE家族有遗传易感性的单倍型,但FcγRⅡB和FcγRⅢA基因在SLE的遗传易感性中可能对立发挥作用。

Objective To analyze the genetic predisposition of immunoglobulin receptor( FcγR)ⅡB and ⅢA genes polymorphisms and systemic lupus erythematosus( SLE) in Xinjiang Uygur Autonomous Region. Methods The polymorphisms in FcγR ⅡB and ⅢA genes in human immunodeficiency virus( human) chromosome 2,region 3( 1q23)were determined by polymerase chain reaction and restriction fragment length polymorphism( PCR-RFLP). General epidemiological data and DNA blood samples from 103 patients from Xinjiang Uyghur pedigrees( including 87 Xinjiang Uyghur SLE core pedigrees) were analyzed using pedigree-relatedness( FBAT). Allele and genotype analysis of 13 functional single nucleotide polymorphisms in the FcyR IIB and Ⅲ A genes of selected SLE nuclear families were performed. Results The pedigree association analysis showed that only two single nucleotide polymorphisms( rs10917661 and rs1050501) in FcγRⅡB gene were important susceptibility loci for SLE. Only two single nucleotide polymorphisms( rs403016 and rs28888) in FcγRⅢA gene were important genetic predisposition sites for SLE. Haplotype analysis showed that only 50 Ter-225 Thr-FcγRⅡB haplotype as well as 72 Arg-118 Asn-FcyRⅢA haplotype were associated with SLE susceptibility. In the FcγRⅡB and FcγRⅢA genes,no haplotypes were found to be susceptible to SLE,indicating that polymorphisms in FcγRⅡB and FcγRⅢA genes may play a role in the genetic predisposition for SLE. Conclusion Haplotypes in FcyRⅡB and FcyRⅢ A were identified to be susceptible to SLE in SLE families from Xinjiang Uygur Autonomous Region. Moreover,the FcyRⅡB and FcyRⅢA genes may play a role in the genetic susceptibility for SLE in general.