D4S1647、D6S2414基因座在中国汉族、蒙古族、藏族的遗传多态性

目的 调查D4S1647、D6S2414基因座在中国汉族、蒙古族、藏族群体中的遗传分布规律。方法 采集308份血及唾液标本应用PCR技术，扩增产物用非变性聚丙酰胺凝胶电泳分离，银染显色分析。结果 两位点各群体基因型频率分布均符合Hardy-Weinberg平衡，每一位点等位基因频率分布在各群体间无显著差异；通过对10个汉族家系的遗传模式分析，证实了两位点等位基因传递遵循孟德尔遗传规律。结论 D4S1647、D6S2414基因座在中国汉族，蒙古族，藏族群体均具有高度遗传多态性。     

血管紧张素转换酶基因与中国人群冠心病、高血压病及糖尿病的关系

目的：研究血管紧张素转换酶(ACE)基因与中国人群冠心病(CHD)、高血压病(EH)及2型糖尿病(T2DM)的关系。方法：250例呈不同组合的EH、T2DM以及CHD患者及90例正常对照用改良的聚合酶链反应(PCR)方法检测ACE基因型，比较基因型及等位基因频率分布。结果：①无合并CHD的T2DM及EH组ACE基因型及等位基因频率与正常对照无显著差异；②CHD组无论是否合并EH及／或T2DM，Ⅲ基因型及Ⅰ等位基因频率均显著低于正常对照，而DD基因型及D等位基因频率均显著高于正常对照；③T2DM合并CHD组及EH合并CHD组中Ⅱ基因型及Ⅰ等位基因频率均显著低于正常对照，而DD基因型及D等位基因频率均显著高于正常对照。结论：ACE基因多态性与中国人群CHD相关。这种关联亦见于EH或T2DM合并CHD中，但ACE基因仅是CHD发病的遗传学基础，而与是否合并EH及／或T2DM无关。     

纤溶酶原激活物抑制物-1基因4G/5G基因型分布频率与心肌梗死和脑梗死相关性初步分析

目的研究我国汉族人纤溶酶原激活物抑制物-1基因启动子区-675位4G/5G(单鸟嘌呤核苷酸插入/缺失)基因多态性与心肌梗死和脑梗死的等位基因特异性的相关性.方法以等位基因特异性聚合酶链反应(AS-PCR)扩增56例心肌梗死患者,54例脑梗死患者,83例无关健康对照个体的基因组DNA,鉴定PAl-1 4G/5G基因型及分布频率,常规方法检验研究个体的主要临床和生化指标.结果PAI-1基因启动子区4G/5G基因多态性在心肌梗死,脑梗死患者组中的分布频率与对照组明显不同.在心肌梗死组中,4G/4G基因型分布频率(71.40%)比对照组(30.12%)显著增加(P＜0.001),杂合型4G/5G基因型分布频率(25.00%)比对照组(62.65%)明显降低;而在脑梗死组中,4G/4G,4G/5G基因型分布频率(分别为20.37%,55.56%)均比对照组(分别为30.12%,62.65%)低,5G/5G基因型明显增加(24.07%vs7.32%,P＜0.001).而且心梗组中血浆PAI-1活性水平随着4G等位基因的减少而降低;脑梗死组中,血浆PAI-1活性水平随着5G等位基因的升高而增加.心肌梗死、脑梗死患者组中的血浆PAI-1活性水平,甘油三酯水平和血糖水平都比对照组明显升高(分别为P＜0.001,P＜0.05,P＜0.001).结论本研究表明,中国汉族人PAI-1基因启动子区4G/5G基因多态性可能和心肌梗死、脑梗死发生的危险性相关,4G/5G基因多态性可能是一种重要的遗传性血栓性疾病的危险因子.     

中国蒙,汉族酒依赖与醇脱氢酶和醛脱氢酶基因多态性的相关研究

为探讨醇脱氢酶（ＡＤＨ）基因和醛脱氢酶（ＡＬＤＨ）基因多态性与酒依赖患病的相互关系，用耳血干血痕聚合酶链反应、等位基因特异性寡核苷酸探针方法，检测乙醇代谢酶ＡＤＨ和ＡＬＤＨ基因型在我国蒙、汉民族酒依赖与非酒依赖者中分布频率。结果显示在酒依赖组（汉族５２例，蒙族３１例）与正常对照组（汉族４８例，蒙族３５例）之间：汉族的ＡＬＤＨ２基因型频率与等位基因频率的分布差异有非常显著性（Ｐ＜０．０１），而蒙族则表示为ＡＤＨ２基因型频率与等位基因频率的分布差异有非常显著性（Ｐ＜０．０１）。这提示汉族酒依赖的发病与ＡＬＤＨ２基因有关，蒙族则与ＡＤＨ２基因有关。     

乳腺癌组织P21WAF1基因多态性与蛋白表达的关系

目的 :探讨乳腺癌组织p2 1WAF1DNA多态性与蛋白表达的关系。方法 :分别采用聚合酶链反应单链构象多态性技术 (PCR -SSCP)和免疫组化S -P法检测 10 0例乳腺癌石蜡包埋组织和 4 0例乳腺良性病变组织p2 1WAF1DNA多态性和蛋白表达。结果 :18% (18/ 10 0 )的乳腺癌组织和 5 % (2 / 4 0 )对照组组织分别出现两种p2 1WAF1DNA多态性 ,前者明显高于后者 ,组间有显著差异 (χ2 =3 94 ,P <0 0 5 ) ;5 0 % (5 0 / 10 0 )的乳腺癌组织和 12 5 % (5 / 4 0 )对照组组织表达p2 1WAF1蛋白 ,前者明显高于后者 ,组间有显著差异 (χ2 =16 84 ,P <0 0 1) ;10 0 % (18/ 18例 )的具有p2 1WAF1DNA多态性的乳腺癌组织p2 1WAF1蛋白表达阳性 ,39% (32 / 82 )的无p2 1WAF1DNA多态性乳腺癌组织蛋白表达阳性 ,p2 1WAF1DNA多态性组明显高于无多态性组 ,组间有显著差异 (χ2 =2 1 95 ,P <0 0 1) ;p2 1WAF1DNA多态性与p2 1WAF1蛋白表达呈正相关 (r =0 5 76 ,P <0 0 1)。结论 :乳腺癌组织p2 1WAF1DNA多态性可能产生不同的转录本并生成相应的蛋白质分子。     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

CYP2A6基因多态性对丙戊酸钠血药浓度的影响

目的探讨细胞色素P4502A6(CYP2A6)基因多态性对丙戊酸钠血药浓度的影响。方法选择单药服用丙戊酸钠的癫患者98例,应用巢式PCR(nested-primerpolymerasechainreaction)方法分析其CYP2A6基因型,分析等位基因CYP2A6*1及CYP2A6*4;同时应用荧光偏振免疫法(FPIA)测定患者丙戊酸钠的血药浓度。结果98例患者中CYP2A6基因型为*1/*1者73例(74·5%),*1/*4者24例(24·5%),*4/*4者1例(1·0%),根据基因型分为A组(CYP2A6*1/*1)和B组(CYP2A6*1/*4或CYP2A6*4/*4)。B组患者丙戊酸钠的标准血药浓度平均值(4·1393±0·2793)较A组(3·3486±0·3919)高,差异有统计学意义(P<0·05)。结论CYP2A6基因多态性影响丙戊酸钠的血药浓度,含有CYP2A6*4等位基因的患者应用丙戊酸钠应较常规降低用量。     

变形链球菌F-ATP酶亚基基因uncA遗传多态性的研究

目的研究变形链球菌临床分离株耐酸因子F—ATP酶亚基α的结构基因uncA的遗传多态性，并探讨基因多态性与细菌耐酸力及龋病发生的关系。方法分别从高龋、无龋个体中分离变形链球菌34和30株，其中包括18株高耐酸株、20株低耐酸株。从细菌组DNA扩增uncA，行限制性内切酶长度多态性分析（RFLP）及核酸测序比较。结果不同限制性内切酶RFLP产生不同的基因型，测序证实了导致多态出现的基因变异；内切酶Hph Ⅰ产生的A、B基因型在不同患龋个体分离菌株的分布不同（P〈0．05），A型uncA在高龋分离株的检出率高于无龋分离株；内切酶MboⅡ产生的C、D基因型在不同耐酸力菌株中的分布不同（P〈0．05），C型uncA在高耐酸力菌株的检出率高于低耐酸力菌株。结论变形链球菌F—ATP酶的α亚基基因uncA具有明显遗传多态性，酸性环境下生存力强的菌株可能出现基因的适应性变异，不同基因型uncA分布与菌株的耐酸力及致龋力相关。     

PPP1R3基因Asp905Tyr多态性与安徽汉族人2型糖尿病相关性研究

目的研究 1型蛋白磷酸酶骨骼肌特异的糖原靶向调节亚单位基因 (PPP1R3) Asp90 5 Tyr多态性与安徽汉族人 2型糖尿病 (T2 DM)相关性。方法选取安徽省合肥地区汉族 T2 DM患者 2 6 2例 ,健康成人 10 4例 ,运用聚合酶链反应限制性酶切片段长度多态性技术 (PCR- RFL P)进行基因型测定。以体质指数 (BMI) 2 5为分割点 ,将病例组和对照组进行分层分析。结果 1PPP1R3基因 Asp90 5 Tyr多态性与安徽汉族人 2型糖尿病没有明显的相关性。 2以 BMI<2 5基因型Tyr/ Tyr组为参照组 ,BMI≥ 2 5携有 Asp90 5等位基因个体的糖尿病发病风险明显增加 (OR=3.6 9;95 % CI:1.38～ 8.89;P=0 .0 0 6 )。结论 PPP1R3基因 Asp 90 5 Tyr多态性可能不是安徽省汉族人 2型糖尿病主要的致病因素。肥胖与 Asp90 5等位基因间的交互作用可增加糖尿病的发病风险。     

Single Nucleotide Polymorphisms in the Human Gene for Osteoprotegerin are Not Related to Bone Mineral Density or Fracture in Elderly Women

Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50–0.64, C1217T P = 0.51–1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61–0.66, C1217T P = 0.14–0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.