HLA-DM基因多态性调查及其与HLA-DRB_1基因的连锁分析

目的:探讨贵州地区汉族人群HLA-DM基因多态性分布,并分析其与HLA-DRB1基因间是否存在连锁不平衡关系。方法:用多聚酶链反应限制性片段长度多态性技术分析106例贵州地区汉族正常人的HLA-DM基因型;同时用序列特异性引物PCR技术检测其HLA-DRB1基因型。结果:贵州地区汉族人群中DMA*0101～0103等位基因频率分布依次为0.745、0.231和0.024,DMA基因型0101/0101和0101/0102频率分布较高者(分别为0.547和0.349);DMB*0101～0104等位基因频率分布依次为0.547、0.165、0.217和0.071,DMB基因型频率分布较高者依次为0101/0101、0101/0102和0101/0103(频率分别为0.311、0.208和0.189);DMA*0102与DRB1*08及DMA*0102与DRB1*12之间连锁不平衡参数分别为2.09和5.07。结论:贵州地区汉族人群中HLA-DM等位基因频率分布以HLA-DMA*0101～0102、HLA-DMB*0101～0103为主,DM基因型分布以DMA*0101/0101、0101/0102和DMB*0101/0101、0101/0102、0101/0103为主;贵州地区汉族人群中HLA-DM基因与HLA-DRB1基因之间存在连锁不平衡关系。     

尖锐湿疣患者HLA-DM基因多态性研究

目的探讨尖锐湿疣（CA）患者的HLA-DM基因的多态性，寻找可能的易感基因。方法运用PCR-RFLP方法确定98例CA患者和93例正常人群中HLA-DM的基因型。分析DM与CA的关联性。结果检测到7种DMA与DMB等位基因，HLADMA＊0101和DMB＊0101等位基因在汉族CA患者中的频率显著性增高（P〈0．05和P〈0．01），而DMA＊0102等位基因在CA患者中的频率显著性降低（P〈0．01）。DMA和DMB基因型在CA与正常对照之间无显著性差别。结论HLADMA＊0101和DMB＊0101等位基因可能是汉族人CA的易感基因或与易感基因连锁。     

广西籍汉族SLE患者与HLA-DQA1等位基因的相关性研究

目的 探讨广西籍汉族系统性红斑狼疮(SLE)及狼疮性肾炎(LN)患者与人类白细胞抗原-DQA1(HLA-DQA1)等位基因的相关性.方法 用聚合酶链式反应-序列特异性引物法(PCR-SSP)对64例广西籍汉族SLE患者及60例汉族健康人群的HLA-DQA1频率进行检测和相关分析.结果 在广西籍汉族人群中检出 HLA-DQA1*0101、0102、0103、0104、0201、0301、0302、0401、0501、0601共10个亚型;SLE 组 HLA-DQA1*0101、0102 等位基因频率较正常对照组显著升高(χ2 =8.627,P=0.003,RR=3.421及χ2=8.965,P=0.003,RR=3.314);LN组HLA-DQA1*0102等位基因频率较无LN表现的SLE组显著升高(χ2 =6.418, P=0.011,RR=4.688);LN组HLA-DQA1*0501 等位基因频率较无LN表现的SLE组显著降低(χ2 =6.130,P=0.013,RR=0.172);未发现与LN病理类型显著相关的HLA-DQA1等位基因.结论 DQA1*0101、0102可能是广西汉族 SLE 的易感基因;DQA1*0102可能是广西汉族LN的易感基因,HLA-DQA1*0501可能是广西汉族LN的保护基因.     

类风湿关节炎患者的HLA-DM基因多态性分析

目的:探讨我国汉族类风湿关节炎(RA)患者的HLA-DM(DMA和DMB)基因的多态性及与临床的相关性.方法:应用多聚酶链反应/序列特异性寡核苷酸探针(PCR/SSOP)检测 96 例RA患者及 100 名正常人HLA-DM基因第三外显子多态性,并应用PCR/限制性片段长度多态性分析(PCR/RFLP)筛选HLA-DRB*0405 阳性个体.结果:类风湿关节炎患者和正常人群的DM等位基因均以DMA*0101 和DMB*0101 为主(分别为 86 5% 和 87 5%,及 85 0% 和 90 0%).DM各等位基因表型频率在RA组和正常对照组之间均无显著性差异.HLA-DRB1*0405阳性的RA组与正常对照组之间也无显著性差异.DRB1*0405阳性率、RF滴度在DMB*0101组显著高于DMB*0102组(P值分别小于0 01和0 05).结论:DM基因多态性可能不影响RA的易感性,但在一定程度上可能对RA病情及活动性有重要影响.     

脾胃湿热证与人类白细胞抗原Ⅱ类基因多态性的相关性研究

【目的】探讨广东地区汉族人群慢性胃炎、消化性溃疡患者中脾胃湿热证与人类白细胞抗原(HLA)-Ⅱ类等位基因的相关关系。【方法】选择以籍贯为广东地区的汉族健康人(正常对照组16例)和慢性浅表性胃炎或消化性溃疡患者(观察组46例,根据辨证分为脾胃湿热证组26例、脾气虚证组20例)的全血为研究标本,采用聚合酶链反应—序列特异性引物(PCR-SSP)基因分型方法检测HLA-Ⅱ类基因中的HLA-DQB1、HLA-DRB1、HLA-DQA1及HLA-DPB1的等位基因类型。【结果】DQA1*0103基因型在脾胃湿热组显著高于正常对照组(P<0.05),但与脾气虚组比较无显著性差异;DQA1*0505基因型在脾胃湿热组显著低于正常对照组及脾气虚组(P<0.05)。【结论】脾胃湿热证存在着一定的免疫遗传基础,DQA1*0103基因型可能是脾胃湿热证的易感基因,DQA1*0505可能是脾胃湿热证的保护性基因。     

SLE病人及其子代与SLE相关基因及抗体关系研究

目的探讨缓解期系统性红斑狼疮(SLE)病人所生子女罹患SLE的危险性。方法应用实时定量PCR技术检测14例SLE病人、病人子女及18例对照者HLA-DRB1*1501、DRB1*0301、DQA1*0102、DQB1*0602的频率,免疫印迹法检测入组者ENA抗体谱。结果 SLE病人组DQA1*0102频率显著高于对照组(RR=2.02,P<0.05),而两组间DRB1*1501、DRB1*0301、DQB1*0602频率比较差异无显著意义(P>0.05);SLE病人组DQB1*0602频率显著高于其子女组(RR=2.06,P<0.05),而两组间DRB1*1501、DRB1*0301、DQA1*0102频率比较差异无显著性(P>0.05);SLE子女组DQA1*0102频率显著高于对照组(RR=2.14,P<0.05);而两组间DRB1*1501、DRB1*0301、DQB1*0602频率比较差异无显著性(P>0.05)。SLE病人组自身抗体SSA及dsDNA出现频率明显高于对照组(P=0.019、0.015),两组间SSB及Ro-52差异无显著性(P>0.05);SLE病人子女组所测自身抗体检出率为0。结论 HLA-DQA1*0102为SLE的易感等位基因,DQA1*0102有一定的遗传倾向。经过系统治疗达到缓解期的SLE病人生育的子女罹患SLE的危险性无明显增加趋势。     

安徽汉族51例免疫性不育症中医证型与HLA-DQA1基因型的关系

目的:探讨抗精子抗体阳性的免疫性不育症患者与人类白细胞抗原-DQA1(Human LeococyteAntigen-DQA1,HLA-DQA1)基因的相关性及不同中医证型与HLA-DQAl等位基因的相关性。方法:采用聚合酶链反应序列特异性引物(polymerase chain reaction-sequence specific primer,PCR-SSP)技术,将51例抗精子抗体阳性的免疫性不育症中医分型为肾阴不足型、湿热内蕴型和瘀血阻滞型的患者与60名正常健康人的HLA-DQA1基因进行分型研究。结果:免疫性不育症组HLA-DQA1*0401等位基因频率明显高于正常对照组(χ2=29.869,P<0.01),免疫性不育症组DQA1*0301等位基因频率较正常对照组显著降低(P<0.01)。肾阴不足型免疫性不育症组HLA-DQA1*0301基因频率较正常对照组显著降低(P<0.01)。HLA-DQA1*0401基因频率较正常对照组显著升高(P<0.01)。结论:HLA-DQA1*0401等位基因可能是抗精子抗体阳性的免疫性不育症的易感基因,DQA1*0301可能是安徽汉族免疫性不育症的保护基因;免疫性不育症患者的中医证型肾阴不足型可能与DQA1*0401有关。     

类风湿关节炎患者的HLA—DM基因多态性分析

目的：探讨我国汉族类风湿关节炎（RA）患者的HLA－DM（DMA和DMB）基因的多态性及与临床的相关性。方法：应用多聚酶链反应。序列特异性寡核苷酸探针（PCR／SSOP）检测96例RA患者及100名正常人HLA－DM基因第三外显子多态性，并应用PCR／限制性片段长度多态性分析（PCR／RFLP）筛选HLA-DRB*0405阳性个体。结果：类风湿关节炎患者和正常人群的DM等位基因均以DMA＊0101和DMB＊0101为主（分别为86．5％和87．5％，及85．0％和90．0％）。DM等各位基因表型频率在RA组和正常对照组之间均无显著性差异。HLA－DRB1＊0405阳性的RA组与正常对照组也无显著性差异。DRB1＊0405阳性率、RF滴度在DMB＊0101组显著高于DMB＊0102组（P值分别小于0．01和0．05）。结论：DM基因多态性可能不影响RA的易感性，但在一定程度上可能对RA病情及活动性有重要影响。     

中国北方汉族人群白细胞抗原DRB1及DQA1区基因多态性与乙型肝炎病毒感染结局的关系

目的探讨中国北方汉族人群白细胞抗原(HLA)DRB1及DQA1区等位基因多态性与乙型肝炎病毒(HBV)感染不同结局的关系,分析基因—环境交互在慢性乙肝发生中的作用。方法采用病例—对照研究(慢性乙肝患者207人,HBV携带者212人,自限性HBV感染者148人)方法,比较3组人群检测的HLA等位基因频率并应用交互相乘模型分析基因—环境交互作用。结果慢性乙肝组HLA-DQA1*0301等位基因频率(14·81%)显著低于HBV携带组(25·24%)和自限性HBV感染组(25·00%)(Pc=0·002;Pc=0·007);自限性HBV感染组HLA-DQA1*0102等位基因频率(8·78%)显著高于HBV携带组(1·89%)和慢性乙肝组(2·18%)(Pc=0·000;Pc=0·000);自限性HBV感染组HLA-DQA1*0302等位基因频率(4·05%)显著低于慢性乙肝组(11·41%)(Pc=0·005)。经多元logistic回归分析调整年龄、性别、吸烟和饮酒的混杂效应后,HLA-DQA1*0302仍是发展为慢性乙肝的危险因素(OR=3·913,P=0·0006),HLA-DQA1*0102和HLA-DQA1*0301是HBV感染后的保护因素(OR=0·200,P=0·0004;OR=0·258,P=0·0000)。饮酒与HLA-DQA1*0102[交互指数(Ⅱ)=1·49]、HLA-DQA1*0302(Ⅱ=12·12)在慢性乙肝的发生中可能存在正交互作用,与DQA1*0301存在负交互作用(Ⅱ=0·78)。结论携带HLA-DQA1*0302等位基因者感染HBV后可能增加慢性乙肝发生的风险,而携带HLA-DQA1*0301和HLA-DQA1*0102者可能降低慢性乙肝发生的风险;基因—环境交互作用可能影响HBV感染的结局。     

HLA-DQA1基因多态性与儿童Graves''病的相关性研究

目的:分析重庆地区汉族儿童Graves'病(Graves'disease,GD)与人类白细胞抗原DQA1基因(HLA-DQA1)多态性的相关性.方法:用聚合酶链反应-单链构象多态性(PCR-SSCP)及DNA测序方法,对已经确诊的重庆汉族GD患儿85例和正常对照组50名儿童的外周血白细胞基因组DNA的HLA-DQA1基因多态性进行分析.结果:在GD组和对照组中检测到7种单链构象,分别标为a b c d ef g带型.GD组中d(HLA-DQA1*0102)、f(HLA-DQA1*0302/0501)两带型频率(分别为43.5%,VS 8.0%;27.0%VS 8.0%)显著高于正常对照组(χ2=18.79,P=0.001,RR=8.86;χ2=6.80,P=0.009,RR=4.27),而b带型(HLA-DQAt*0101/0301)频率(8.2%VS 52.0%)显著低于正常对照组(χ2=29.43,P＜0.001,RR=0.08).结论:HLA-DQA1*0102和HLA-DQA1*0302/0501可能与GD易感性相关,而HLA-DQA1*0101/0301可能与GD的保护性相关.提示上述3基因位点可能分别是重庆地区汉族儿童GD的易感基因和保护基因.     

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

湖南地区汉族系统性红斑狼疮患者HLA—DM多态性研究

目的：探讨湖南地区系统性红斑狼疮患者的遗传易感性基因,方法：运用PCR－SSO方法分析SLE患者和正常人群中HLADM基因的多态性。结果：正常人群和SLE人群组中,DMA＊0101及DMB＊0101频率占主要地主。DMA＊0104和DMB＊0104为罕见基因,两组之间无显著性差异。结论：湖南地区SLE患者中未发现HLADM易感基因。     

HLA-DM polymorphism and risk of trichloroethylene induced medicamentosa-like dermatitis

Objective To establish the association between genetic polymorphisms of HLA-DMA and HLA-DMB and risk of developing trichloroethylene-induced medicamentosa-like dermatitis （TIMLD）. Methods Sixty-one cases were medically confirmed to have been affected with TIMLD and 60 controls were selected from exposed workers who were free from TIMLD The TIMLD cases and controls were similar in terms of age, sex, and duration of exposure. DNA was extracted both from the TIMLD cases and controls, HLA-DMA and HLA-DMB loci were amplified by using Touchdown PCR, and the alleles and genotypes were confirmed by restriction fragment length polymorphism （RFLP） and direct sequencing. Finally, the frequencies of HLA-DMA and HLA-DMB variants were compared between the two groups. Results The results showed that the frequency of HLA-DMA＊0101 and HLA-DMB＊0103 alleles was significantly increased in TIMLD patients than in controls （71.3% wv. 55.0% for HLA-DMA＊0101; P〈0.05） （11.5% vs. 3.3% for HLA-DMB＊0103; P〈0.05）. In addition, the frequency of HLA-DMA＊0102-＊0102 homozygous genotype was also significantly higher in the controls than in the patients （25.0% wv. 8.2%, P〈0.05）, whereas the frequency of heterozygous HLA-DMB ＊0101-＊0102 genotype was lower in the patients in comparison with the controls. Conclusion The polymorphisms of HLA-DM may be associated with the susceptibility to TIMLD.     

1型糖尿病患者胰岛自身抗体与人类白细胞抗原-DQ基因型的关系

目的 探讨急性起病1型糖尿病（T1DM）患者谷氨酸脱羧酶抗体（GADA）、蛋白酪氨酸磷酸酶抗体（IA-2A）、胰岛素自身抗体（IAA）与人类白细胞抗原（HLA-DQ）基因型之间的关系。方法采用横断面、病例对照研究方法,495例T1DM患者与376例正常对照用放射配体法检测GADA和IA-2A,其中使用胰岛素在2周以内的71例患者与300例正常对照检测IAA。187例抗体阳性、151例抗体阴性T1DM患者与278例正常对照采用PCR直接测序法确定HLA-DQ基因型。结果（1）与正常对照比较,T1DM患者（n=187）DQA1＊03-DQB1＊0303、DQA1＊05-DQB1＊0201与DQA1＊03-DQB1＊0401单体型频率增高（分别为32．6％vs21．9％,14．1％vs3．5％与10．2％vs2．9％,均P〈0．01）,DQA1＊0102-DQB1＊0602单体型频率降低（1.7％vs5．3％,P〈0．05）,而DQA1＊03-DQB1＊0302频率差异无统计学意义（4．7％vs3．8％,P〉0．05）。（2）在338例T1DM患者中,携带DQA1＊05-DQB1＊0201与DQA1＊03-DQB1＊0401单体型患者,GADA阳性率高于不携带此单体型者（分别为55．8％vs41．0％与65．5％vs40．3％,P〈0．05或P〈0．01）;携带DQA1＊03-DQB1＊0303单体型患者IA-2A阳性率高于不携带此单体型者（27．0％vs7．9％,P〈0．01）;携带DQA1＊03-DQB1＊0302单体型患者GADA与IA-2A阳性率分别与不携带此单体型者比较,差异均无统计学意义（48．5％vs43．9％与24．2％vs15．4％,P〉0．05）;而携带保护性DQA1＊0102-DQB1＊0602单体型患者GADA阳性率低于不携带此单体型者（16．7％vs45．9％,P〈0．05）。携带易感单体型者IAA检出率与不携带者比较,差异均无统计学意义（P〉0．05）。结论1型糖尿病患者GADA与DQA1＊05-DQB1＊0201、DQA1＊03-BQB1＊0401单体型相关,IA-2A与DQA1＊03-DQB1＊0303单体型相关。     

HLA-DR-DQ单倍型与类风湿关节炎的相关性研究

目的　探讨DR -DQ单倍型与我国汉族人群类风湿关节炎 (RA)发生的关系。方法　以 10 0名健康人为对照 ,采用PCR -RFLP法对汉族人群中 35例RA患者的DRB1、DRB3、DRB5、DQA1和DQB1基因位点多态性进行分析。结果　DRB1 0 4 0 5 -DQA1 0 30 1-DQB1 0 4 0 1单倍型频率在RA患者中明显高于正常人 (分别为 14 %和 4 5 % ,RR =3 97,P <0 0 1) ,该单倍型阳性RA患者的病情重于其它RA患者 ,包括关节肿胀数、晨僵时间、RF滴度和病情严重例数在阳性组明显高于阴性组 (P <0 0 5 ) ;而DRB1 15 0 1-DRB5 0 10 1-DQA1 0 10 2 -DQB1 0 6 0 2单倍型频率在正常人明显高于RA患者 (分别为 12 %和 4 3% ,P <0 0 1)。结论　DRB1 0 4 0 5 -DQA1 0 30 1-DQB1 0 4 0 1单倍型与RA发病及病情严重程度相关 ;而DRB1 15 0 1-DRB5 0 10 1-DQA1 0 10 2 -DQB1 0 6 0 2单倍型则可能对易患RA起保护作用     

HLA-DQ, DR allele polymorphism of type 1 diabetes in the Chinese population: a meta-analysis

Background Type 1 diabetes （TID） is a multifactorial disease. This article aims to evaluate the relationship between allele polymorphism of HLA-DQ, DR and TID in the Chinese population. Methods The odds ratios （ORs） of HLA-DQ, DR allele distributions in patients with T1D were analyzed against healthy controls. All the relevant studies in Pubmed and CNKI were identified, and poor qualified studies were excluded. The meta-analysis software REVMAN 4.2 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. The publication bias were also evaluated. Results DQA1＊0301, DQA1＊0501, DQB1＊0201, DQB1＊0302 were the susceptible alleles （all P 〈0.05） in the Chinese population, their merger ORs 2.40, 3.15, 3.66, and 2.67 respectively. DQA1＊0103, DQA1＊0201, DQA1＊0401, DQB1＊0301, DQB1＊0402, DQB1 ＊0501, DQB1＊0503, DQB1＊0601 and DQB1＊0602 were the protective alleles （P 〈0.05）, their merger ORs were 0.11, 0.45, 0.30, 0.38, 0.23, 0.37, 0.25, 0.48, and 0.30 respectively. In serum level, DR3, DR4, DR9 alleles were the susceptible alleles （all P 〈0.05） and their merger ORs were 5.58, 1.53, 1.66, 29.78, and 6.65 respectively. HLA-DR2, DR5, and DR7 alleles were the protective alleles （all P 〈0.05） and their merger ORs were 0.39, 0.51, and 0.50. In genetic type level, DRB1＊04, DRB1＊0301, DRB1＊0901 were the susceptible alleles （all P 〈0.05） and their merger ORs were 2.19, 6.43, 1.31, 3.83, and 8.08. DRBI＊07, DRBI＊08, DRB1＊12, DRB1＊13, DRB1＊14, DRB1＊16, DRBI＊0406 alleles were the protective alleles （all P 〈0.05） and their merger ORswere 0.44, 0.27, 0.45, 0.13, 0.19, 0.40, and 0.27 respectively. Conclusions In the Chinese population, some HLA-DQ, DR alleles are relevant to T1D which are not totally the same as non-Chinese populations.     

广东地区妇女子宫平滑肌瘤遗传易感性与HLA-DRB1、DQA1、DQB1相关性的研究

目的分析子宫平滑肌瘤与ＨＬＡ－ＤＲＢ１、ＤＱＡ１、ＤＱＢ１等位基因的相关性,从而探讨子宫平滑肌瘤患者的遗传易 感性。方法　用ＰＣＲ－ＳＳＰ及ＰＣＲ－ＳＳＯ技术对５１例外科手术后病理证实为子官平滑肌瘤患者和５０例正常妇女进行 ＨＬＡ－ＤＲＢ１、ＤＱＡ１、ＤＱＢ１等位基因的基因分型。结果　ＨＬＡ－ＤＲＢ１＊０２,ＤＱＡ１＊０６０１在子宫平滑肌瘤组明显高于对照 组（Ｐ＜０．０５,ＲＲ＝５．３７８,１５．４）,而ＤＲＢ１＊０１、＊０７,ＨＬＡ－ＤＱＡ１＊０ｌ０２却表现为对照组增高（Ｐ＜０．０５,ＲＲ＝０．２２５,０．３７５, ０．３２９）。结论ＤＲＢ１＊０２、＊０１、＊０７,ＨＬＡ－ＤＱＡ１＊０６０１、＊０１０２基因与子宫平滑肌瘤的遗传易感性相关联。