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
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摘要
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.
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.
引文
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[16]李红梅,刘水和,叶震璇,等.Ⅰ型干扰素通路IRF5基因多态性与系统性红斑狼疮的关联性研究[J].中国免疫学杂志,2017,33(4):574-578.
[17]鄢海波,赵令,马宁,等.汉族人系统性红斑狼疮和狼疮肾炎与IL-22受体基因多态性的关系[J].中国现代医学杂志,2017,27(9):44-48.
[18]裘影影,何建强,汤郁,等.间充质干细胞对系统性红斑狼疮患者树突状细胞的免疫抑制作用[J].江苏大学学报(医学版),2015,25(6):477-481.
[19]陈向华,王建吉,耿学丽,等. Tim-1蛋白表达及其基因多态性与系统性红斑狼疮患者营养功能的相关性[J].中国医科大学学报,2017,46(7):623-627.
[20]于海燕,王晓春,王燕铭,等. FcγRⅡA基因多态性与牙周炎关系的研究进展[J].现代生物医学进展,2016,16(13):2593-2595.
[21]Chua KH,Lian LH,Sim XJ,et al. Association between PDCD1 gene polymorphisms and risk of systemic lupus erythematosus in three main ethnic groups of the Malaysian population[J]. Int J Mole Sci,2015,16(5):9794-9803.
[22]方欣臣,孙自敏.杀伤细胞免疫球蛋白受体配型在造血干细胞移植中的应用[J].国际输血及血液学杂志,2017,40(1):30-34.
[23]张昀,刘淑芬,曾学军.中国汉族人群FcγRIIIA F158V基因多态性与系统性红斑狼疮及狼疮肾炎相关[J].基础医学与临床,2017,37(5):709-713.
[2]张燕,张成丽,陈博,等. HSD17B1 rs676387和SHBG rs6259基因多态性与四川汉族人群SLE的关联性[J].中国皮肤性病学杂志,2015,29(4):257-360.
[3]杨宇峰,朱剑,茹晋丽,等.系统性红斑狼疮380例外周血淋巴细胞亚群变化及临床意义[J].解放军医药杂志,2015,27(5):69-72.
[4]崔晓丽,李红梅,刘水和,等. IRF2基因rs13146124位点多态性与系统性红斑狼疮的关联性研究[J].重庆医学,2016,45(30):4230-4232.
[5]李晓岚,钟华,李明,等. TNFAIP3和TNIP1基因多态性与系统性红斑狼疮临床表型的相关性分析[J].中国皮肤性病学杂志,2015,29(12):1216-1220.
[6]吴成将,袁秋然,莫益姣,等. CD40基因多态性及血清水平与系统性红斑狼疮发病机制的相关研究[J].中华皮肤科杂志,2016,49(1):12-16.
[7]Pradhan V,Surve P,Rajadhyaksha A,et al. Mannose binding lectin(MBL)2 gene polymorphism&its association with clinical manifestations in systemic lupus erythematosus(SLE)patients from western India[J]. Indian J Med Res,2015,141(2):199-204.
[8]韦叶生,蓝艳.白细胞介素-21基因多态性及血清水平与系统性红斑狼疮的相关性研究[J].微循环学杂志,2015,32(4):43.
[9]来炳祺,殷晓艳. klotho蛋白在心力衰竭合并肾损伤中的表达及其临床意义[J].解放军医药杂志,2016,28(4):78-81.
[10]吴凌燕,谢正德,刘亚丽,等.中国北方汉族人群杀伤细胞免疫球蛋白样受体及其配体HLA-Ⅰ基因的多态性研究[J].中华医学遗传学杂志,2015,32(5):651-656.
[11]朱准,聂英坤.免疫球蛋白G的Fc段受体ⅡB在自身免疫病中的研究进展[J].中华风湿病学杂志,2016,29(2):135-137.
[12]焦银生,李会娟.系统性红斑狼疮实验室检查研究进展[J].临床误诊误治,2015,28(3):109-112.
[13]李晓岚,钟华,李明,等. TNFAIP3和TNIP1基因多态性与系统性红斑狼疮临床表型的相关性分析[J].中国皮肤性病学杂志,2015,12(12):1216-1220.
[14]Shahin RM,El KE,Khalifa RH,et al. Contribution of Tolllike receptor 9 gene single-nucleotide polymorphism to systemic lupus erythematosus in Egyptian patients[J]. Immunol Invest,2016,45(3):235-314.
[15]李媛,李萍,陈华,等. HLA-DQB1基因多态性与中国汉族人群系统性红斑狼疮的相关性[J].标记免疫分析与临床,2015,22(1):37-40.
[16]李红梅,刘水和,叶震璇,等.Ⅰ型干扰素通路IRF5基因多态性与系统性红斑狼疮的关联性研究[J].中国免疫学杂志,2017,33(4):574-578.
[17]鄢海波,赵令,马宁,等.汉族人系统性红斑狼疮和狼疮肾炎与IL-22受体基因多态性的关系[J].中国现代医学杂志,2017,27(9):44-48.
[18]裘影影,何建强,汤郁,等.间充质干细胞对系统性红斑狼疮患者树突状细胞的免疫抑制作用[J].江苏大学学报(医学版),2015,25(6):477-481.
[19]陈向华,王建吉,耿学丽,等. Tim-1蛋白表达及其基因多态性与系统性红斑狼疮患者营养功能的相关性[J].中国医科大学学报,2017,46(7):623-627.
[20]于海燕,王晓春,王燕铭,等. FcγRⅡA基因多态性与牙周炎关系的研究进展[J].现代生物医学进展,2016,16(13):2593-2595.
[21]Chua KH,Lian LH,Sim XJ,et al. Association between PDCD1 gene polymorphisms and risk of systemic lupus erythematosus in three main ethnic groups of the Malaysian population[J]. Int J Mole Sci,2015,16(5):9794-9803.
[22]方欣臣,孙自敏.杀伤细胞免疫球蛋白受体配型在造血干细胞移植中的应用[J].国际输血及血液学杂志,2017,40(1):30-34.
[23]张昀,刘淑芬,曾学军.中国汉族人群FcγRIIIA F158V基因多态性与系统性红斑狼疮及狼疮肾炎相关[J].基础医学与临床,2017,37(5):709-713.