阿尔茨海默病易感性与HLA—DR基因的相关性

目前 ,多数学者认为阿尔茨海默病(Ａｌｚｈｅｉｍｅｒ’ｓｄｉｓｅａｓｅ ,ＡＤ)是一种中枢神经系统退变性疾病。在ＡＤ众多病因的研究中 ,比较肯定的 2种因素是遗传和增龄 ,最近研究显示炎症作用和免疫反应可能是ＡＤ的重要发病机制 ,而ＨＬＡ ＤＲ基因属于人类免疫应答基因系统 ,因此 ,研究ＨＬＡ ＤＲ基因可从免疫和遗传 2种角度阐明多因素所致的免疫炎症反应在ＡＤ患者中枢神经退变过程中的作用机制 ,从而深入了解ＡＤ的确切发病机制。1　ＨＬＡ ＤＲ基因[1]　　编码人类白细胞抗原 (ｈｕｍａｎｌｅｕｋｏ ｃｙｔｅａｎｔｉｇｅｎ ,ＨＬ…     

上海地区Ⅰ型自身免疫性肝炎与HLA-DRB1等位基因的相关性研究

目的 分析HLA－DRB1等位基因与上海地区I型自身免疫性肝炎（AIH）的相关性，探讨AIH的遗传易感背景。方法 采用序列特异性多聚酶链反应（PCR－SSP），对32例I型AIH患者和48例健康对照者进行HLA－DRB1等位基因及有关基因亚型的分析。结果 HLA－DR4基因频率在I型AIH患者中较健康对照组显著增高[46.9%与20.8%；相对危险度（RR）＝3．35，χ^2=5.99,P=0.014]。其他等位基因在两组间差异无显著性。进一步对HLA－DR4等位基因亚型的分析表明，I型AIH患者组DRB1^*0405的基因频率较健康对照组有增加趋势（21．9％与6．3％，χ^2=4.23,P=0.04，但Pc=0.08)。HLA－DRβ分子的第3等位基因高变区第71位精氨酸残基的频率在I型AHI患者中显著增高（46.9%与18.8%,χ^2=7.14,P=0.008)。结论 上海地区I型AIH的发病与HLA－DR4以及HLA－DRB1第3高变区DR7位精氨酸残基相关。     

HLA-DRB基因多态性与发作性睡病

目的 探讨人类白细胞抗原（ＨＬＡ）－ＤＲＢ等位基因在发作性睡病发病中的作用。方法 对１０例发作性睡病患者和５０例正常对照的ＨＬＡ－ＤＲＢ等位基因进行分型,用序列特异性引物体外基因扩增法分析ＨＬＡ－ＤＲＢ特异性。结果 根据临床表现和多次小睡潜伏时间试验诊断的发作性睡病患者其ＨＬＡ－ＤＲＢ１＊１５０１和ＨＬＡ－ＤＲＢ５＊０１０１均阳性,而在正常对照组,其等位基因频率分别为１７％和４４％,两者差异具显著     

青藏高原藏族人群HLA-DRB1基因与包虫病遗传抗性关联研究

目的确定青藏高原地区藏族人群包虫病患者的人类白细胞抗原-DRB1(Human leukocyte antigen-DRB1,HLADRB1)等位基因中易感基因和抗性基因,为研究藏族人群包虫病的感染机制及遗传特点提供依据。方法本研究采用病例对照法。病例组选取青海省玉树和果洛藏族自治州的世居藏族囊型包虫病63例和泡型包虫病73例;对照组选取该地区无血缘关系的藏族健康人,共计60例。应用聚合酶链反应-直接碱基序列基因分型(PCR-SBT)技术,比较等位基因频率。结果泡型和囊型包虫病病例组HLA-DRB1*04等位基因频率均小于对照组(χ2=4.71、4.31,P均0.05)。结论HLA-DRB1*04等位基因与青藏高原藏族人群囊型和泡型包虫病相关联,对其感染有保护作用,是其抗性基因。     

Graves病白细胞减少易感性与HLA-DRB1基因多态性的关联

目的探讨天津地区汉族Graves病(GD)白细胞减少易感性与HLA-DRB1基因多态性的关联.方法采用聚合酶链反应-序列特异性引物(PCR-SSP)方法检测45例GD白细胞减少患者、50例GD白细胞正常患者和90名正常对照的HLA-DRB1等位基因频率.结果(1)在不考虑白细胞变化的情况下,GD患者DRB1*08基因频率明显高于对照组(P＜0.01,RR=2.62),DRB1*07基因频率明显低于对照组(P＜0.01,RR=0.24).(2)GD白细胞减少组DRB1*08(P＜0.01,RR=4.17)和DRB1*15(P＜0.05,RR=1.69)基因频率较对照组显著增高,DRB1*07基因频率明显低于对照组(P＜0.01,RR=0.13).(3)GD白细胞减少组DRB1*08基因频率(P＜0.01)和DRB1*15基因频率(P＜0.05)均明显高于白细胞正常组,DRB1*09(P＜0.05)基因频率明显低于白细胞正常组.结论天津地区汉族GD白细胞减少易感性与HLA-DRB1*08,HLA-DRB1*15基因频率增加有关;GD的保护性与HLA-DRB1*07基因频率减少有关.     

HLA-DRB1、-DQB1基因多态性与食管鳞癌遗传关联性

目的　从基因水平探讨食管鳞癌HLA DRB1 , DQB1等位基因的遗传易感性 ,以阐述其免疫遗传学特征。方法　运用序列特异性引物聚合酶链反应技术 ,检测无亲缘关系湖北汉族健康人 1 36例、食管鳞癌患者 42例的HLA DRB1 , DQB1等位基因。结果　湖北汉族人食管鳞癌患者与正常人比较 ,HLA DRB1 0 90 1等位基因分布频率显著增高 (0 .2 50 0比 0 .1 397,P =0 .0 2 8,OR =2 .0 53 ,病因分数 =0 .1 2 82 ) ,HLA DQB1 0 30 1基因分布频率显著增高 (0 .2 976比 0 .1 875 ,P =0 .0 4 6 ,OR =1 .835 ,病因分数 =0 .1 35 4)。两者间其余HLA DRB1、 DQB1等位基因分布频率差异均无显著性。结论　HLA DRB1 0 90 1及 DQB1 0 30 1等位基因均与食管鳞癌正关联 ,为其易感基因。该两等位基因测序结果与其基因库第 2外显子序列吻合。     

HLA—DR.DQ基因与骨关节结核的易感性研究

目的 探讨ＨＬＡ－ＤＲ．ＤＱ基因多态性与骨关节结核的遗传关联性,比较骨关节结核与肺结核之间易感基因的差异。方法 采用聚合酶链反应－序列特异性引物（ＰＣＲ－ＳＳＰ）方法,对８６例骨关节结核。８８例正常人及３４例肺结核的ＨＬＡ－ＤＲ．ＤＱ等位基因进行分析。结果 骨关节结核组与正常人比较,骨关节结核组ＤＲＢ１＊０９、ＤＱＢ１＊０３０１基因频率增高（３８．９９％比８．２４％ ＰＣ〈０．０００１ＲＲ＝８．９     

HLA-DRB1高分辨基因分型在造血干细胞移植中的意义探讨

目的 探讨造血干细胞移植中进行供－受体ＨＬＡ－ＤＲＢ１高分辨基因分型的重要作用,并对ＨＬＡ－ＤＲＢ１等位基因频率在中国人群中的分布进行分析。方法 采用美国莱姆达公司提供的微量ＳＳＰ＾ＴＭ ＨＬＡ－ＤＲＢ１ ＰＣＲ－ＳＳＰ低分辨及高分辨分型试剂盒对１０１例造血干细胞移植供－受体进行高分辨基因分型,其中供－受体３７对,无关个体５０例。结果 在３７例供－受体分型中,对２对为低分辨ＨＬＡ－ＤＲＢ２位点相合     

HLA-DRB1和肿瘤坏死因子α基因多态性与肝硬化的遗传易感性

目的探讨HLA-DRB1和肿瘤坏死因子(TNF)α基因多态性与肝硬化遗传易感性之间的关系.方法应用聚合酶链反应-序列特异性引物法、限制性片段长度多态性等技术检测106例乙型肝炎后肝硬化患者和108例健康对照者的HLA-DRB1和TNFα基因多态性.结果肝硬化组HLA-DRB1*120X等位基因频率比对照组显著升高(35.9%比11.1%,P＜0.001),TNFα中TNF2/1基因型频率比对照组明显升高(19.8%比10.2%, P＜0.05),DRB1*150X等位基因频率明显低于对照组 (13.2%比30.6% ,P＜0.05),分层分析表明,DRB1*120X等位基因与肝硬化的关联大于TNF2等位基因.结论 HLA-DRB1*120X和TNF2等位基因与乙型肝炎后肝硬化的遗传易感性相关,携带这2个等位基因的个体发生肝硬化的危险性增加.HLA-DRB1*120X等位基因可能是肝硬化的易感基因,HLA-DRB1*150X等位基因为抗性基因.     

Relationship between HLA‐DPA1 mRNA expression and susceptibility to hepatitis B

Chronic hepatitis B virus (HBV) infection is influenced by both viral and host factors. In genome‐wide association studies, the human leucocyte antigen HLA‐DPA1 and related polymorphism rs3077 were found to be associated with susceptibility to and spontaneous clearance of HBV infection. Here, we evaluated the association between HLA‐DPA1 mRNA expression and the risk of HBV infection. HLA‐DPA1 and rs3077 polymorphisms were investigated in 169 patients with chronic HBV and 217 healthy controls (HCs) from Sichuan Han blood donors using sequence‐based typing and meta‐analysis for HLA‐DPA1 alleles. HLA‐DPA1 mRNA levels were measured by real‐time polymerase chain reaction. The results showed that HLA‐DPA1 and rs3077 were associated with HBV infection in the Sichuan population. Rs3077T and DPA1*01:03 played protective roles in HBV infection, and rs3077C and DPA1*02:02 increased susceptibility to HBV infection. We found that the HLA‐DPA1 mRNA expression was decreased in the CHB group; in particular, the 3077CT, 3077TT, DPA1*01:03 and DPA1*02:01 alleles showed a significant decrease. Our results demonstrated, for the first time, that expression of HLA‐DPA1 alleles and rs3077 affected the risk of HBV infection. Genotypes with lower HLA‐DPA1 expression had a greater susceptibility to HBV infection. Thus, further independent studies are needed to strengthen the associations of these polymorphisms with susceptibility to and clearance of HBV infection in Chinese populations.     

干扰素α抗病毒治疗效果与人白细胞抗原-DRB1*11基因单核苷酸多态性的相关性

目的 探讨人白细胞抗原-DRB1*11基因片段内5个干扰素α调节区间单核苷酸多态性的分布与慢性乙型肝炎患者对干扰素α治疗效果的关系. 方法 采用回顾性分析研究方法 ,随机抽取107例慢性乙型肝炎患者在我院经过干扰素α治疗12个月,已停药6个月的患者,分持续应答组(A组)和非持续应答组(B组).在美国国立生物技术信息中心上查询人乙型肝炎病毒X蛋白结合蛋白基因位点,使用DNA池技术测序作单核苷酸多态性位点的验证,针对各个单核苷酸位点分别设计引物和TaqMan-MGB探针,检测5个干扰素α调节区的单核苷酸多态性,分析两组间的差异.结果 107例慢性乙型肝炎患者对干扰素a持续应答的30例,非持续应答的77例,持续应答组5个干扰素α调节区中基因型CT的占有率为18.0%,AG为10.8%,非持续应答组基因型CT的占有率为23.8%,AG为15.8%,持续应答组CT、AG这两对基因型的占有率比非持续应答组低,两组比较,x2值分别为7.728和7.956,P＜0.05,差异有统计学意义,其余基因型之间比较,差异无统计学意义.结论 检测干扰素调节基因,可粗略评估患者对干扰素应答的状况,有助于临床医师预测患者对干扰素α的疗效.     

Association of the HLA-DRB1 gene with susceptibility to aortoarteritis in a Chinese Han population.

Aortoarteritis is a chronic inflammatory disease mainly affecting the aorta and its major branches. Recent immunogenetic studies indicate that certain human leucocyte antigen (HLA) alleles are significantly associated with aortoarteritis in several populations. The purpose of the present study was to investigate the relationship between the HLA-DRB1 alleles and aortoarteritis in a Chinese Han population. HLA-DRB1 genotypes were identified by PCR-SSP and PCR-RFLP in 84 Chinese patients with aortoarteritis and 102 healthy Chinese controls. It was found that the HLA-DRB1*04 allele (38.1% in patients vs. 15.7% in controls, p<0.001, relative risk (RR)=2.43) and the HLA-DRB1*07 allele (47.6% vs. 10.8%, p<0.001, RR = 4.42) were significantly associated with aortoarteritis. Furthermore, there was no significant difference in the frequency of the DRB1*0405 subtype between the patient and control groups. Thus the susceptibility to aortoarteritis in this Chinese Han population was closely related with the HLA-DRB1*04 and DRB1*07 alleles. Thus individuals with the HLA-DRB1*04 and DRB1*07 alleles may be at higher risk for developing aortoarteritis.     

Relationship between IFN-γ gene polymorphism and susceptibility to intrauterine HBV infection

AIM: To explore the susceptibility of children to intrauterine HBV infection by studying the relationship between IFN-γ gene polymorphism, including IFN-γ+874A/T single nucleotide polymorphism(SNP) and CA repeat microsatellite polymorphism and intrauterine HBV infection.METHODS: A TaqMan fluorescence polymerase chain reaction in the IFN-γ+874A/T single nucleotide polymorphism was tested in the intrauterine HBV infection group(group Ⅰ) and the normal immune children group(group Ⅱ). Capillary electrophoresis was performed in the above two groups to assay the IFN-γ CA repeat microsatellite polymorphism.RESULTS: Frequencies of AA, AT and TT genotypes were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group, respectively. A significant difference was found in the frequency distribution of IFN-γ+874 genotype between the two groups (χ2 = 5.102,P = 0.02389). In the intrauterine HBV infection group the AA genotype was more common than in the normal immune group. Frequency of IFN-γ+874A allele was 77.17% in the intrauterine HBV infection group, and 60.27% in the normal immune children group. In the intrauterine HBV infection group the IFN-γ+874A allele was more common than in normal immune group.A significant difference was found in the frequency distribution between the two groups (χ2= 7.238,P= 0.02389, OR= 2.228, 95% CI = 1.244-3.992).(CA12)+/(CA12)+ of IFN-γ CA microsatellite polymorphism was 11.90% in the intrauterine HBV infection group and 26.47% in the normal immune children group.A significant difference was found in the frequency distribution between the two groups (χ2= 5.64, P =0.0176). Frequency of IFN-γ CA repeat was 25% in the intrauterine HBV infection group and 43.38% in the normal immune children group. The frequency of IFN-γ CA repeat was less in the intrauterine HBV infection group than in normal immune group. A significant difference was found in the frequency distribution between the two groups (χ2 = 7.548, P= 0.0060).CONCLUSION: There is a relationship between IFN-γ+874A/T SNP and intrauterine HBV infection as well as between IFN-γ CA microsatellite polymorphism and intrauterine HBV infection. IFN-γ gene polymorphism might be important in determining individual's susceptibility to intrauterine HBV infection.     

Relationship between IFN-γ gene polymorphism and susceptibility to intrauterine HBV infection

AIM: To explore the susceptibility of children to intrauterine HBV infection by studying the relationship between IFN-gamma gene polymorphism, including IFN-gamma+874A/T single nucleotide polymorphism (SNP) and CA repeat microsatellite polymorphism and intrauterine HBV infection. METHODS: A TaqMan fluorescence polymerase chain reaction in the IFN-gamma+874A/T single nucleotide polymorphism was tested in the intrauterine HBV infection group (group I) and the normal immune children group (group II). Capillary electrophoresis was performed in the above two groups to assay the IFN-gamma CA repeat microsatellite polymorphism. RESULTS: Frequencies of AA, AT and TT genotypes were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group, respectively. A significant difference was found in the frequency distribution of IFN-gamma+874 genotype between the two groups (chi2 = 5.102, P = 0.02389). In the intrauterine HBV infection group the AA genotype was more common than in the normal immune group. Frequency of IFN-gamma+874A allele was 77.17% in the intrauterine HBV infection group, and 60.27% in the normal immune children group. In the intrauterine HBV infection group the IFN-gamma+874A allele was more common than in normal immune group. A significant difference was found in the frequency distribution between the two groups (chi2 = 7.238, P = 0.02389, OR = 2.228, 95% CI = 1.244-3.992). (CA12)+/(CA12)+ of IFN-gamma CA microsatellite polymorphism was 11.90% in the intrauterine HBV infection group and 26.47% in the normal immune children group. A significant difference was found in the frequency distribution between the two groups (chi2 = 5.64, P = 0.0176). Frequency of IFN-gamma CA repeat was 25% in the intrauterine HBV infection group and 43.38% in the normal immune children group. The frequency of IFN-gamma CA repeat was less in the intrauterine HBV infection group than in normal immune group. A significant difference was found in the frequency distribution between the two groups (chi2 = 7.548, P = 0.0060). CONCLUSION: There is a relationship between IFN-gamma+874A/T SNP and intrauterine HBV infection as well as between IFN-gamma CA microsatellite polymorphism and intrauterine HBV infection. IFN-gamma gene polymorphism might be important in determining individual's susceptibility to intrauterine HBV infection.     

乙醛脱氢酶基因多态性与酒精性肝病的关系

目的 观察乙醛脱氢酶(ALDH)基因多态性与山东地区汉族人群酒精性肝病的关系,探讨酒精性肝病遗传学的发病机制。 方法 采用聚合酶链反应结合内切酶酶切及电泳技术,检测山东地区汉族人群中酒精性肝病组、嗜酒组和对照组(各20例)中ALDH各基因型及等位基因的频率并进行比较。结果ALDH2*1、ALDH2*2两种等位基因在对照组与酒精性肝病组之间的分布差异有显著性(x2=4.80,P<0.05),对照组与无肝病嗜酒组之间差异无显著性,在嗜酒组和酒精性肝病组中以ALDH2*1/*1基因型为主,均未检出纯合子的ALDH2*2/*2。 结论 ALDH基因多态性与酒精性肝病的发生关系密切。等位基因ALDH2*2可能是本地区汉族人群中嗜酒和酒精性肝病的负性危险因素。     

中国藏族PSCA基因rs2294008多态性与胃癌遗传易感性的关系

目的:研究前列腺干细胞抗原基因(prostatestem cell antigen gene,PSCA)rs2294008位点多态性与中国藏族胃癌患者遗传易感性的关系.方法:收集185例藏族胃癌患者与200例健康人群的外周血样本,提取基因组DNA,采用dHPLC方法进行PSCA基因rs2294008位点分型.结果:PSCA基因rs2294008位点3种基因型C C、C T、T T在胃癌病例组中频率分别为:40.00%、48.65%和11.35%,而在对照组中分别为54.00%、39.50%和6.50%.与CC型比较,携带CT,TT型基因型者胃癌发生的危险性增加,OR值分别为1.66(95%CI 1.09-2.54)和2.36(95%CI 1.11-5.00).结论:PSCA基因rs2294008位点CT,TT基因型增加中国藏族人群的胃癌易感性.     

抗SSA和SSB抗体与HLA-Ⅱ基因的相关性分析

目的：探讨云南汉族系统性红斑狼疮（SLE）患者抗SSA和SSB抗体与HLA－DRB1、DQA1、DQB1等位基因及单体型的相关性。方法：采用多聚酶链反应－序列特异性引物（PCR－SSP）技术对63例云南汉族SLE患者和54名同民族健康对照进行DRB1、DQA1、DQB1基因分型。结果：云南汉族SLE患者中DR15（P＜0．01）、DR16（P＜0．05）、DQA1＊0102（P＜0．05）、DQA1＊0103（P＜0．01）、DQB1＊0601（P＜0．05）等位基因频率明显增高；抗SSA和SSB抗性阳性的SLE病人中DQA1＊0103频率均显著增高（P＝0．042，P＝0．006）；抗SSB抗体阳性的SLE患者中的DQA1＊0501 频率均显著增高（P＝0．009）。结论：云南汉族SLE 抗SSA和SSB抗体的产生与DQA1＊0103等位基因相关；抗SSB抗体的产生还与DQA1＊0501相关。     

NOS1基因多态性与湖北汉族人变应性哮喘易感性的关系

目的　研究一氧化氮合成酶结构式基因 (NOS1)第 2 9外显子翻译终止位点下游 2 76 bp处 C/ T(C5 2 6 6 T)位点多态性与湖北汉族人变应性哮喘易感性及血浆 Ig E水平的关系。方法　用聚合酶链反应和限制片段长度多态性 (PCR- RFL P)方法对湖北汉族 134例变应性哮喘患者 (哮喘组 )及 90例无血缘关系的汉族健康人(对照组 )进行 NOS1基因 C5 2 6 6 T位点多态性分析 ,用免疫发光法测定血浆总 Ig E水平。结果　哮喘组 NOS1基因 C5 2 6 6 T位点 TT基因型频率与对照组相比差异显著 (P=0 .0 0 9) ,T等位基因频率与对照组相比无显著性差异 (P>0 .0 5 )。哮喘组 TT基因型者血浆总 Ig E显著高于 CC和 CT基因型者 (P<0 .0 5 )。结论　 NOS1基因C5 2 6 6 T位点 TT基因型与湖北汉族人哮喘易感性和高血浆总 Ig E水平均相关。