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.     

新疆维吾尔族HLA-DQA1基因多态性与乙型肝炎病毒感染结局相关性研究

目的 探讨新疆维吾尔族人类白细胞抗原(HLA)-DQA1区等位基因多态性与乙型肝炎病毒(HBV)感染临床转归的相关性.方法 应用序列特异性引物-聚合酶链反应技术(PCR-SSP)对70 例慢性乙型肝炎患者,46 例HBV携带者,42 例HBV感染后自然恢复者,80例健康献血员进行HLA-DQA1基因分型,并比较DQA1多态性的分布频率及其差异.结果 HBV感染后自然恢复组与健康对照组HLA-DQA1*0102分布频率高于慢性乙型肝炎组和HBV携带者组,差异均有统计学意义(P<0.05);HBV携带者组HLA-DQA1*0501分布频率高于健康对照组,差异有统计学意义(P<0.05);慢性乙型肝炎组HLA-DQA1*0501分布频率高于HBV感染后自然恢复组与健康对照组,差异有统计学意义(P<0.05);其他各等位基因频率在各组间差异无统计学意义.结论 新疆维吾尔族人群中携带HLA-DQA1*0501等位基因者感染HBV后可能会增加慢性乙肝发生的风险,而携带HLA-DQA1*0102者可能会降低慢性乙肝发生的风险.     

内蒙古地区不同民族间HLA-DQA1基因多态性研究

目的：研究内蒙古地区不同民族间HLA-DQA1基因多态性。方法：采用PCR-SSP技术对内蒙古地区蒙古族、鄂温克族、达斡尔族、鄂伦春族和回族各200例中HLA-DQA1等位基因进行型别分析。结果：蒙古族中高频率的HLA-DQA1等位基因是0301、0501和0103;低频率等位基因为0101、0102、0104、0201、0302、0401和0601;鄂温克族中高频率的HLA-DQA1等位基因是0301、0104、0501和0102;低频率等位基因为0201和0103;达斡尔族中高频率的HLA-DQA1等位基因是0301、0104、0501和0102;低频率等位基因为0103、0201、0401和0601;鄂伦春族中高频率的HLA-DQA1等位基因是0301、0104、0501和0102;低频率等位基因为0101、0103、0201和0302;回族中高频率的HLA-DQA1等位基因是0301、0501和0201;低频率等位基因为0101、0102、0103、0401和0601。结论：各民族人群间HLA-DQA1基因分布有其独特性。     

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。     

内蒙古包头地区汉族原发性高血压与HLA-DQA1*0301等位基因的相关性研究

目的探讨内蒙古包头地区汉族人群中原发性高血压与人类白细胞抗原(HLA)-DQA1*0301等位基因的相关性。方法用聚合酶链反应-序列特异性引物(PCR-SSP)技术对原发性高血压患者119例(高血压组)及正常对照组130例进行HLA-DQA1*0301等位基因的检测,并对结果进行分组比较。结果 HLA-DQA1*0301等位基因频率在高血压组为0.403 4,正常对照组为0.376 9,两组频率差异无统计学意义。按性别及有无家族史分组统计HLA-DQA1*0301等位基因频率,各组间差异亦无统计学意义。采用Lo-gistic回归控制了年龄的混杂作用后分析HLA-DQA1*0301基因与高血压发生的关系,结果显示该基因与高血压的发生没有关系。结论内蒙古包头地区汉族人群原发性高血压与HLA-DQA1*0301等位基因可能无相关性。     

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.     

1型糖尿病种HLA-DQA1-DQB1连锁基因的特征研究

目的：探讨HLA-DQA1-DQB1连锁基因单倍体与成人缓慢进展型1型糖尿病（SPIDDM）和速发型1型糖尿病（FPIDDM）的相关性。方法：采用PCR/SSP技术检测本组1型糖尿病中102例SPIDDM患者和130例FPIDDM患者频率。结果：①HLA-DQA1＊0301-DQB1＊0201和DQA1＊0501-DQB1＊0201连锁基因单倍体与SPIDDM（Pc〈0.001）和FPIDDM（Pc〈0.001）均呈显著正相关。②HLA-DQA1＊0301-DQB1＊0301和DQA1＊0301-DQB1＊0602连锁基因单倍体与SPIDDM呈显著正相关（Pc〈0.001）。③HLA-DQA1＊0301-DQB1＊0302、DQA1＊0301-DQB1＊0303及DRB1＊0301-DQA1＊0301-DQB1＊0201连锁基因单倍体与FPIDDM呈显著正相关（均Pc〈0.05）;DQA1＊0102等位基因中SPIDDM组16例（15.69%）;FPIDDM组10例（7.69%）（P〈0.05）;DQA1＊03基因SPIDDM组47例（46.08%）,FPIDDM组79例（60.77%）（P〈0.05）;DQB1＊0601基因SPIDDM组10例（9.8%）,FPIDDM组4例（3.08%）（P〈0.01）。结论：SPIDDM和FPIDDM虽然均为自身免疫性糖尿病,但其HLA表型并不完全相同,不同的HLA表型可能是决定患者起病方式及病情发展不同的因素之一。     

广西沿海地区Graves病与HLA—DQA1、DRB1＊09等位基因的相关性研究

目的:探讨HLA-DQA1和HLA-DRB1*09等位基因在广西沿海地区Graves病(Graves disease,GD)患者中的分布情况及这些基因位点与GD的关系.方法:采用PCR-SSP方法检测广西沿海地区113例GD患者及90例正常人HLA-DQA1、DRB1*09的基因型, 计算和比较2组的HLA- DQA1和 DRB1*09等位基因频率.结果:与正常对照组比较,GD患者组中 HLA-DQA1*0301、0501和 HLA-DRB1*0901的频率明显增高(P<0.05).结论:广西沿海地区GD患者中HLA-DQA1*0301、0501和HLA-DRB1*0901基因出现频率增高,HLA-DQA1*0301、0501和HLA-DRB1*0901可能是该区GD遗传易感基因.     

HLA-DQA1基因与新疆吐鲁番地区维吾尔族2型糖尿病高血压的相关性

目的 探讨新疆吐鲁番地区维吾尔族2型糖尿病(T2DM)高血压与HLA-DQA1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(PCR-SSP)技术,对新疆吐鲁番地区维吾尔族65例正常对照者、42例高血压患者、73例T2DM患者和37例T2DM高血压患者的HLA-DQA1等位基因频率进行检测,分析T2DM高血压HLA-DQA1等位基因多态性.结果 与正常对照组比较,T2DM组HLA-DQA1*0104等位基因频率增高;T2DM高血压组HLA-DQA1*0104、HLA-DQA1*0301、HLA-DQA1*0501等位基因频率增高,差异均有统计学意义(P<0.05).与高血压组比较,T2DM高血压组HLA-DQA1*0104等位基因频率明显增高,差异有统计学意义(P<0.01).结论 HLA-DQA1*0104可能是新疆吐鲁番地区维吾尔族T2DM的易感基因;HLA-DQA1*0104、HLA-DQA1*0301、HLA-DQA1*0501可能是新疆吐鲁番地区维吾尔族T2DM高血压的易感基因.     

子宫内膜异位症合并不孕与HLA—DQA1、DRB1的相关性

目的 探讨HLA-DQA1、DRB1等位基因与子宫内膜异位症患者不孕的相关性。方法 用聚合酶链反应-序列特异性引物（PCR-SSP）对102例经腹腔镜或外科手术证实的子宫内膜异位症患者（其中35名患者合并不孕）进行HLA-DQA1、DRB1等位基因的基因分型并与对照组进行比较。结果 子宫内膜异位症患者HLA1-DQA1*0401等位基因频率显著高于正常对照,HLA1*0301等位基因频率显著低于正常对照。其中,合并不孕者HLA1-DQA1*0301、DRB1*07、DRB1*08/12等位基因频率低于正常对照,HLA1-DRB1*07、DRB1*08/12等位基因频率低于无合并不孕者;而无合并孕者HLA-DQA1*0301,HLA-DRB1*07*08/12可能与子宫内膜异位症的不孕机制相关,HLA1*0401与子宫内膜异位症的发病机制相关,但不参与子宫内膜异位症的不孕机制。]     

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     

湖南汉族群体HLA—DQA1位点等位基因多态性分析

目的：分析湖南汉族群体ＨＬＡ－ＤＱＡ位点等位基因多态性。方法;应用ＰＣＲ／ＳＳＰ和银染ＰＣＲ／ＳＳＣＰ技术对６０名无血缘关系湖南汉族健康个体作ＨＬＡ－ＤＱＡ１基因分型。结果：检出１０种ＨＬＡ－ＤＱＡ１等位基因。基因频率范围为０．０１６７～０．２２５４,ＨＬＡ－ＤＱＡ１＊０３０２,＊０５０１,＊０１０２常见等位基因,ＨＬＡ－ＤＱＡ１＊０１０１,＊０２０１,＊０４０１为少见等位基因。检出２６种基因型,     

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。     

广西壮族不同程度慢乙肝与HLA-DQA1基因相关性研究

目的探讨广西壮族不同程度慢性乙型病毒性肝炎（慢乙肝）的HLA-DQA1等位基因的相关性。方法采用序列特异性引物-聚合酶链式反应（ssp-PCR）法检测壮族轻、中、重度各30例慢乙肝患者HLA-DQA1等位点并进行基因分析研究。结果轻度、中度组HLA-DQA1^＊0103等位基因的频率较重度组明显升高;重度组HLA-DQA1^＊0301等位基因的频率较慢乙肝轻度组明显降低。结论携带DQA1^＊0103等位基因个体感染HBV以后更易发展为轻、中度肝炎,而DQA1^＊0301可能为重度慢乙肝抗性基因。     

皖籍汉人HLA-DQA1、-DQB1基因型与银屑病的相关性研究

目的 探讨ＨＬＡ－ＤＱＡ１＊０１０３、－ＤＱＡ１０２０１、ＤＱＢ１＊０２０１、－ＤＱＢ１＊０３０３四种等位基因与皖籍汉族银屑病患者的相关性。方法 利用聚合酰边反应－序列特异性引物（ＰＣＲ－ＳＳＰ）法。对８４例名健康患者及４０名健康对照进行ＰＣＲ反应,记录以上四种等位基因在他们中的分布情况。结果 （１）ＨＬＡ－ＤＱＡ１＊０２０１与皖籍汉族银屑病患者具有明显的相关性（Ｐｃ＝０．００００１９１,ＯＲ＝８     

Association between HLA-DQA1, -DQB1 gene polymorphisms and susceptibility to asthma in northern Chinese subjects

Objective Human leukocyte antigen (HLA) class Ⅱ genes, especially HLA-DQ genes, which are highly polymorphic, have been thought to be candidate loci for the etiology of asthma, and shown to be involved in antigenic presentation. This study was conducted to investigate whether susceptibility or resistance to asthma is associated with HLA-DQA1 and DQB1 genes polymorphism.Methods Venous blood samples were collected from northern Chinese population with Han ethnic. (1) One hundred and twenty-five unrelated asthmatic individuals and 52 subjects from 12 asthmatic pedigrees. (2) Ninety-six healthy controls without asthma and atopy with the same ethnic. Genomic DNA was extracted using standard phenol-chloroform method. The second exon of HLA-DQA1 and DQB1 genes were amplified by sequence-specific primer-polymerase chain reaction (SSP-PCR) method. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial reversibility by β2-agonist evaluated.Results HLA-DQA1*0104 allele and HLA-DQB1*0201 allele were significantly higher in asthmatics than those in healthy controls (0.408 vs 0.177, P&lt;0.01; 0.568 vs 0.198, P&lt;0.01). Odds ratios (ORs) were 3.203 (95% CI 1.699-6.037), 5.328 (95% CI 2.883-9.849) respectively. Conversely, HLA-DQA1*0301 allele and HLA-DQB1*0301 were significantly decreased in asthmatics compared to healthy controls (0.296 vs 0.50, P&lt;0.01; 0.4 vs 0.563, P&lt;0.05); Logistic regression analysis showed that HLA-DQA1*0104 allele was associated independently with asthma etiology, OR ［represented by Exp(B)］ was 5.0942 with 95% CI 2.2520-21.1813; Spearman’s analysis showed that HLA-DQA1*0104 allele and HLA-DQB1*0201 allele were positively associated with atopy, the correlation coefficient were 0.183 and 0.289 respectively, P&lt;0.01. By contrast, HLA-DQA1*0301 allele was negatively related to atopy, the correlation coefficient was -0.168, P&lt;0.05; linkage analysis did not support the view that HLA-DQA1/DQB1 genes were linked to asthma with LOD value being 0.72.Conclusions HLA-DQA1*0104 allele and HLA-DQB1*0201 allele were implicated in susceptibility to asthma and atopy, HLA-DQA1*0301 allele and HLA-DQB1*0301 might be protective factor against asthma. Asthma and atopy are multifactorial disorders, HLA-DQA1 and DQB1 genes are involved in the regulation of immune specific response to common allergen.     

Relationship between HLA-DQA1 polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy

Background Autoimmune mechanisms are likely to participate in the pathogenesis of subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the major histocompatibility complex may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class Ⅱ genes, especially highly polymorphic HLA-DQ genes, play an important role in the activation of immune responses, and thus control the predisposition for or protect from IDC. This study was conducted to investigate the HLA-DQA1 allele polymorphisms in IDC patients and to explore the underlying immunological mechanism and the hereditary susceptibility to IDC.Methods The polymerase chain reaction sequence-specific primers (PCR-SSP) technique was used to analyze the polymorphisms in the second exon of DQA1 in three groups: 72 IDC patients diagnosed according to the criteria of World Health Organization (IDC group); 100 end-stage heart failure patients suffering from a disease of known etiology (HF group); and 100 healthy subjects enrolled for the study during a routine health survey (control group). Patients in the IDC group were stratified according to ejection fraction (EF). Those with EF values were higher than 35% were placed into subgroup 1; subgroup 2 included patients with an EF value of 15%-35%; and subgroup 3 consisted of those whose EF values less than 15%. Results The frequency of HLA-DQA1＊0501 alleles was significantly higher in the IDC group (0.39) than that in the HF group (0.12) and the control group (0.09) (both P&lt;0.05). Further analysis of the three IDC subgroups showed a higher frequency of DQA1＊0501 among patients with lower EF values (both P&lt;0.05, compared with subgroups 1 and 2). The frequency of DQA1＊0201 was higher in the control group than that in the IDC group (P&lt;0.05).Conclusions The HLA-DQA1＊0501 allele confers susceptibility to IDC, while the DQA1＊0201 allele confers protection against it, which indicates that genetic background involved in IDC and heart failure is different. HLA-DQA1 genes are involved in the regulation of specific immune responses by auto- or foreign anti-myocardium antibody.