中国人II 型糖尿病与 HLA-DQA1 基因的关联研究

应用ＰＣＲ扩增ＨＬＡＤＱＡ１基因第二外显子多态区基因片段，γ３２Ｐ末端标记９个序列特异性寡核苷酸（ＳＳＯ）进行斑点杂交，本文首次对９８例中国人Ⅱ型糖尿病（ＮＩＤＤＭ）与ＨＬＡ的关联进行研究，结果显示ＮＩＤＤＭ全组及常见型亚组０４０１等位基因频率均较正常对照组显著减少，ＰＣ值分别小于０．０１和０．０５，ＲＲ０．２４７，这与ＩＤＤＭ中ＤＱＡ１等位基因频率的变化不同，提示ＮＩＤＤＭ与ＨＬＡ确有关联，但和ＩＤＤＭ发病与ＨＬＡ的关联并不相同。     

HLA—DR—DQ连锁基因单倍体与成人缓慢进展型和速发型1型 …

目的 探讨ＨＬＡ－ＤＲ－ＤＱ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 利用ＰＣＲ／ＳＳＰ技术检测了５２例ＳＰＩＤＤＭ患者、３０例ＦＰＩＤＤＭ患者和１３０例正常人的ＨＬＡ－ＤＲ－ＤＱ连锁基因频率。结果 ①ＨＬＡ－ＤＱＡ１＊０３０１－ＤＱＢ１＊０２０１和ＤＱＡ１＊０５０１－ＤＱＢ１＊０２０１连锁基因单倍体与ＳＰＩＤＤＭ（Ｐｃ〈０．００１）     

中国人Ⅱ型糖尿病与HLA—DQA1基因的关联研究

应用ＰＣＲ扩增ＨＬＡ－ＤＱＡ１基因第二外显子多态区基因片段，γ－＾３２Ｐ末端标记个序列特异性寡核苷酸进行五点杂交，本文首次对９８例中国人Ⅱ型糖尿病与ＨＬＡ的关联进行研究，结果显示ＮＩＤＤＭ全组及常见型亚组０４０１等位基因频率均较正常对照组减少，ＰＣ值分别小于０．０１和０．０５，ＲＲ－０．２４７，这与ＩＤＤＭ中ＤＱＡ１等位基因频率的变化不同，提示ＮＩＤＤＭ与ＨＬＡ确有关联，但和ＩＤＤＭ发病与ＨＬＡ的     

扩张型心肌病HLA－DRB_1基因多态性的研究

借助聚合酶链反应（ＰＣＲ）／序列特异性引物（ＳＳＰ）技术对４２例扩张型心肌病（ＤＣＭ）患者和１６８例正常对照者进行人类白细胞抗原（ＨＬＡ）－ＤＲＢ１基因型分析。结果发现ＤＣＭ组ＨＬＡ－ＤＲＢ１＊１１基因频率与对照组比较明显增高（２６．１９％对１３．１％，Ｐ＜０．０５），其ＲＲ＝２．３６。其他等位基因频率在ＤＣＭ组与对照组间差异无显著性。提示ＨＬＡ－ＤＲＢ１＊１１基因可能与ＤＣＭ有关联。     

HLA-DR-DQ连锁基因单倍体与成人缓慢进展型和速发型1型糖尿病的相关性研究

目的探讨ＨＬＡＤＲＤＱ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。方法利用ＰＣＲ／ＳＳＰ技术检测了５２例ＳＰＩＤＤＭ患者、３０例ＦＰＩＤＤＭ患者和１３０例正常人的ＨＬＡＤＲＤＱ连锁基因频率。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（前二者Ｐｃ＜０．０１，后者Ｐｃ＜０．００１）。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。     

肌糖原合成酶基因多态性与糖尿病及其合并高血压的关系

目的研究肌糖原合成酶基因与非胰岛素依赖型糖尿病（ＮＩＤＤＭ）及其合并高血压的关系。方法采用限制性内切酶Ｘｂａｌ对肌糖原合成酶基因片段的聚合酶链反应（ＰＣＲ）产物酶解的方法，观察１６４例ＮＩＤＤＭ（包括６２例合并高血压病人）的糖原合成酶基因多态性。结果肌糖原合成酶基因型（Ａ１／Ａ１，Ａ１／Ａ２）和等位基因（Ａ１，Ａ２）均与ＮＩＤＤＭ无关，而ＮＩＤＤＭ合并高血压者Ａ２等位基因频率明显高于血压正常的ＮＩＤＤＭ者（Ｐ＜０．０５）。结论糖原合成酶基因多态性作为一种标志，提示与其连锁的基因可能参与ＮＩＤＤＭ病人的高血压的发病。     

中国汉族系统性红斑狼疮某些易感基因的研究

为了探索我国北方汉族人群人类白细胞抗原－ＤＲ（ＨＬＡ－ＤＲ）及肿瘤坏死因子Ｂ（ＴＮＦＢ）等位基因多态性与系统性红斑狼疮（ＳＬＥ）的易感性关系，对１０６例健康人和４５例ＳＬＥ患者的ＨＬＡ－ＤＲ和对８０例健康人及４５例ＳＬＥ患者的ＴＮＦＢ等位基因，采用多聚酶链反应－限制性酶切片段长度多态性（ＰＣＲ－ＲＦＬＰ）法进行分析。结果显示：ＳＬＥ患者中频率显著升高的等位基因有ＤＲ２［Ｐ＜０．０５，相对危险性（ＲＲ）＝１．５６］及ＤＲ３（Ｐ＜０．０１，ＲＲ＝２．６９）。而ＤＲ５和对照相比呈相反结果（Ｐ＜０．０５，ＲＲ＝０．４３）。ＳＬＥ患者ＴＮＦＢ＊２等位基因频率显著增高（Ｐ＜０．０５，ＲＲ＝１．８４）。提示ＤＲ２、ＤＲ３、ＴＮＦＢ＊２可能是易感等位基因或易感等位基因标记，而ＤＲ５是一拮抗等位基因或拮抗等位基因标记。并研究了ＨＬＡ－ＤＲ、ＴＮＦＢ等位基因与患者血浆中Ｓ蛋白和补体５ｂ－９结合物的复合物（ＳＣ５ｂ－９）的水平和多种自身抗体及狼疮肾炎、狼疮肺炎、狼疮脑病等狼疮并发症之间的相关性，发现ＨＬＡ－ＤＲ２基因与狼疮肾炎的发生存在正相关（Ｐ＜０．０５，ＲＲ＝１．３２）。     

ACE基因多态性与胰岛素依赖性糖尿病伴肾病的关系探讨

目的：研究ＡＣＥ基因与ＩＤＤＭ肾病关系。方法：用扩增片段长度多态性方法，分析６８例ＩＤＤＭ患者（其中２４例为ＩＤＤＭ伴肾病者，４４例为ＩＤＤＭ不伴肾病者）和５７例正常人的ＡＣＥ基因插入（Ｉ）／缺失（Ｄ）多态性。结果：ＩＤＤＭ患者和正常人之间ＡＣＥ基因Ｉ／Ｄ多态性频率差异不显著，ＩＤＤＭ伴肾病组Ｄ等位基因频率明显高于ＩＤＤＭ不伴肾病组（Ｐ〈０．０５），ＤＤ基因型也有相同趋势（０．０５〈Ｐ〈０．１）。     

HLA—DR基因与我国北方汉族肺结核的相关性研究

目的 探讨我国北方汉族ＨＬＡ－ＤＲ基因多态性与肺结核（ＰＴＢ）的遗传关联性及其与临床表现的关系。方法 本研究采用联合酶链反应－序列特异性引物（ＰＣＲ－ＳＳＰ）方法,对７４例ＰＴＢ患者及９０例正常人的ＨＬＡ－ＤＲ等位基因进行分型。结果 与对照组相比,ＰＴＢ患者组的ＤＲＢ１＊１５等位基因频率显著增高（３４．３％比１７．０％,Ｐｃ〈０．０５,ＲＲ＝２．９１）,ＨＬＡ－ＤＲＢ１＊１２基因频率增高（１５．４     

ApoAI基因多态性与NIDDM关系的研究

采用限制性片段长度多态性（ＲＦＬＰ）技术，对９０例中国汉族人进行分析，发现载脂蛋白ＡＩ（ＡｐｏＡＩ）Ｍ１等位基因频率在体重指数（ＢＭＩ）≥２４的ＮＩＤＤＭ与ＢＭＩ〈２４的ＮＩＤＤＭ之间、在动脉硬化（ＡＳ）与正常对照组之间均存在显著性差异。此外，ＮＩＤＤＭ件ＡＳ（ＮＡ）的等位基因频率分布与ＮＩＤＤＭ相似，与ＡＳ不同。根据上述结果，认为：ＡｐｏＡＩ基因与ＢＭＩ≥２４的ＮＩＤＤＭ相关联：ＢＭＩ≥２４的Ｎ     

The cathepsin D gene exon 2 (C224T) polymorphism and sporadic Alzheimer's disease in European populations

The cathepsin D gene (CTSD) exon 2 (C224T) polymorphism has been associated with an increased risk for sporadic Alzheimer's disease (AD), but with controversial findings. We studied CTSD exon 2 (C224T) and apolipoprotein E (APOE) genotype frequencies in 168 AD patients and 218 age-matched healthy controls from Southern Italy. No statistically significant differences were found in CTSD allele or genotype frequencies between AD patients and controls, and there were no interactions with sex or APOE genotype. Furthermore, comparing our results with the findings from other European populations, the CTSD*T allele frequency showed a statistically significant increasing trend from Northern to Southern regions of Europe in AD patients and controls (z=2.51, p<.01; z=4.02, p<.001, respectively), with a concomitant inverse trend for CTSD*C allele frequency. The regional differences in CTSD allele frequencies could be related to the different patterns of association between this polymorphism and AD in various European studies.     

阿尔茨海默病和血管性痴呆患者血管紧张素转换酶和载脂蛋白E基因多态性分析

目的　探讨阿尔茨海默病 (AD)及血管性痴呆 (VaD)与血管紧张素转换酶 (ACE)和载脂蛋白E(apoE)基因多态性的关系。方法　应用聚合酶链反应和限制性片段长度多态性方法 ,检测了 2 6例晚发AD患者、5 4例VaD患者和6 8例正常老年人的ACE和apoE基因多态性。结果　AD组中apoE等位基因频率分别为ε2 0 .0 77、ε30 .6 15及ε40 .30 8,VaD组apoE等位基因频率分别为ε2 0 .0 5 6、ε30 .6 85及ε4 0 .2 5 9,AD组和VaD组apoEε4等位基因频率显著高于对照组。ACE基因AD组和VaD组DD型频率高于对照组 ,D等位基因亦高于对照组。结论　ACEDD型、apoEε4可能是AD及VaD发病的危险因素     

老年痴呆患者血清及脑脊液载脂蛋白E含量的变化

目的评价Ａｌｚｈｅｉｍｅｒ病（ＡＤ）及多梗塞性痴呆（ＭＩＤ）患者血清及脑脊液（ＣＳＦ）中载脂蛋白Ｅ（ａｐｏＥ）含量变化的临床意义。方法用圆周免疫扩散法测定ＡＤ１４例、ＭＩＤ１８例及对照组１８例的血清ａｐｏＥ含量，同时测定部分患者ＣＳＦ中ａｐｏＥ含量，作对比分析。结果ＣＳＦ中ａｐｏＥ含量，ＡＤ组为０．３４±０．１０ｇ／Ｌ，明显低于对照组的０．５２±０．１６ｇ／Ｌ（Ｐ＜０．０５），ＡＤ组与ＭＩＤ组（０．４３±０．０８ｇ／Ｌ）、ＭＩＤ组与对照组间差异无显著性（Ｐ＞０．０５）；血清中ａｐｏＥ在３组间差异无显著性（Ｐ＞０．０５）。结论ＣＳＦ中ａｐｏＥ含量降低对ＡＤ的诊断及鉴别诊断可能有重要意义。     

IL-6启动子多态性与阿尔茨海默氏病的相关性探讨

目的 探讨细胞因子白介素6(IL—6)与阿尔茨海默氏病(AD)的相关性。方法 用PCR—RFLP技术检测356例英国AD患者和434例对照者IL-6启动子-174C／G多态性，并进行了对比分析。结果 IL-6启动子-174C／G多态性与AD无相关性。其与AD发病年龄、β淀粉样蛋白沉积量和小神经胶质细胞含量无明显相关性。结论 IL-6启动子-174C／G多态性不是AD的危险因素。     

血浆纤溶酶原激活物抑制因子基因启动子多态性与2型糖尿病伴发冠心病的关系

目的从分子遗传水平进行基因多态性研究，以探讨２型糖尿病易伴发冠心病的内在原因。方法对８１例２型糖尿病患者、９３例非糖尿病（非ＤＭ）患者进行口服糖耐量试验、血脂分析、血浆纤溶酶原激活物抑制因子（ＰＡＩ１）基因多态性分析。结果２型糖尿病和非ＤＭ相比ＰＡＩ１基因启动子４Ｇ频率明显增加（４２％和３１％，Ｐ＜０００１）；２型糖尿病伴冠心病与不伴冠心病相比，ＰＡＩ１基因启动子４Ｇ频率及４Ｇ／４Ｇ基因型频率存在明显差异（５２％和３０％，３２％和１４％；Ｐ分别＜０００１、００５）；非２型糖尿病伴冠心病与不伴冠心病相比，ＰＡＩ１基因启动子４Ｇ频率及４Ｇ／４Ｇ基因型频率则无明显差异（３１％和３１％，８％和１６％，均为Ｐ＞００５）。结论ＰＡＩ１基因４Ｇ等位基因可能是糖尿病合并冠心病的内在危险因素     

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Type 2 diabetes (T2D) and Alzheimer??s disease (AD) are two progressive disorders with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF-??) and apolipoprotein E (ApoE) genes might be associated with both T2D and AD, representing possible genetic markers for the development of the AD in subjects with T2D. The aim was to determine ApoE and G-308A TNF-?? gene polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD, 196 T2D patients and 456 healthy controls. Patients with AD had higher frequency of ApoE4 allele compared to T2D patients and controls. The significant association, observed between ApoE2 allele and T2D, disappeared after the data were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF-?? gene polymorphism were similar among the patients with AD, T2D and healthy controls. In conclusion, these results do not support the hypothesis that the A allele of G-308A TNF-?? gene polymorphism is associated either with AD or T2D. Our data confirm the association between the ApoE4 allele and AD, and point out the E2 allele of ApoE gene as the possible risk factor for T2D.     

阿尔茨海默病患者HMG—CoA还原酶基因多态性与血脂关系的研究

目的探讨3-羟-3甲基戊二酰辅酶A（HMG—CoA）还原酶基因多态性与阿尔茨海默病（AD）的关系。方法用PCR—RFLP方法分析HMG—CoA还原酶第2内含子区ScrF1酶切多态性。结果ScrF1酶切多态性基因型频率、等位基因A、a频率在组间比较差异无显著性（P〉0．05），但基因型为AA的AD患者，其总胆固醇（TC）水平显著高于基因型为aa的AD患者（P〈0．01）。结论HMG-CoA还原酶ScrF1酶切多态性与AD无相关性，但患者组AA基因型与TC水平密切相关。     

血管紧张素原M235T基因多态性对血压影响的研究

目的：研究血管紧张素原基因（ＡＧＴ）第二外显子Ｍ２３５Ｔ等位基因的多态性与高血压之间的关系。方法： 应用多聚酶链反应（ＰＣＲ）结合限制性酶切方法对１０５例健康体检者与１０２例原发性高血压（ＥＨ）患者进行基因突变的检测。结果：（１）ＥＨ患者Ｔ２３５ 等位基因频率（０．４４５）高于对照组（０．３２３）,Ｐ＜ ０．０５。在男性ＥＨ患者与男性对照组中差别更为明显（Ｐ＜ ０．０１）;（２）在有家族史的ＥＨ 患者中,Ｍ２３５Ｔ 突变基因型（ＴＴ型）频率高于正常对照组（４２．１％ ＶＳ１８．８％ ,Ｐ＜０．０５）。结论：（１）ＡＧＴ基因的突变与ＥＨ的发病具有相关性。对男性ＥＨ影响可能更大;（２）在有家族史的高血压患者中, ＡＧＴ２３５的ＴＴ基因型与ＥＨ有关     

Interleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer's disease: geographic allele and genotype variations in Europe

The interleukin 6 (IL-6) gene in humans is located in the short arm of chromosome 7 and has a-174 G/C polymorphism in its promoter region. The C allele at position-174 in the promoter of the interleukin 6 (IL-6) gene has been associated with reduced gene expression and reduced plasma levels of IL-6. Given the supposed role of several inflammatory mediators in neurodegeneration and Alzheimer's disease (AD), the IL-6-174 G/C promoter polymorphism has been associated with AD with contrasting findings. First aim of the present study was to investigate whether there was evidence in Southern Italy of an association between the IL-6-174 G/C promoter polymorphism and AD. Secondly, we also tested a possible effect of geographic genetic variations on existing reported associations comparing our results with the findings from published studies on other European populations. We examined apolipoprotein E (APOE) and IL-6-174 G/C promoter polymorphisms in a cohort of 168 sporadic AD patients and 220 sex- and age-matched nondemented controls from Southern Italy. No differences have been found in the IL-6-174 G/C promoter allele and genotype frequencies between AD patients and controls nor in early- and late-onset subsets of AD patients. No statistically significant differences in frequencies between IL-6-174 G/C promoter alleles and AD among APOE allele strata were found. Finally, comparing our results with the findings from other European populations, the IL-6*G/*G genotype frequency showed a statistically significant increasing trend from Northern to Southern regions of Europe in AD patients and controls, with a concomitant increase in IL-6*C/*G genotype frequency. Furthermore, an increasing geographical trend from North to South was found for the IL-6*G allele, with a concomitant inverse trend for IL-6*C allele. We suggest that regional European differences in genotype and allele frequencies of the IL-6-174 G/C promoter polymorphism may explain in part controversial findings on this polymorphism in AD in various European studies.     

对氧磷酶1基因Gln192Arg多态性与阿尔茨海默病的相关性分析

目的 探讨中国汉族人群中对氧磷酶1（PON1）基因Gln192Arg单核苷酸多态性（SNP）与阿尔茨海默病（AD）的相互关系。方法采用实时定量PCR技术检测521例AD患者和578例健康老年人PON1基因Gln192Arg位点SN-P的分布,并通过OR做疾病关联分析。结果AD组（Q／R＋R／R）基因型频率较对照组低,统计分析差异有统计学意义（X^2=4．68,P=0．03）;等位基因频率差异也存在统计学意义,AD组R等位基因频率明显低于对照组（X^2=3．85,P=o．05）。logistic回归分析表明,调整年龄和性别的影响后,（Q／R＋R／R）基因型患AD的危险性是Q／Q基因型的0．71倍（P=0．044,95％CI=0．51～0．99）。结论中国汉族人群中PON1基因Gln192Arg位点R等位基因可能是AD的保护因素。