血管紧张素转换酶基因多态性与冠心病发病的相关关系

目的:从分子遗传学角度分析血管紧张素转换酶(ACE)基因I/D多态与中国北方汉族人群中冠心病发病的相关关系。方法:本研究收集在沈阳军区总医院心内科住院的行冠脉造影检查的病例为研究对象,冠脉动脉照影检查显示冠状动脉主支狭窄程度大于等于70%的入选为冠心病组,冠状动脉照影检查显示冠状动脉主支狭窄程度小于20%的为对照组,共入选568名冠心病患者以及性别与年龄相匹配的529名对照个体为研究对象,利用测序的方法分析检测血管紧张素转换酶(ACE)基因I/D多态在冠心病组与对照组中的频率分布情况。结果:血管紧张素转换酶(ACE)基因I/D多态基因型频率符合Hardy-Weinberg定律。血管紧张素转换酶(ACE)基因I/D多态(II型,ID型和DD型)在我们入选的568例冠心病组分布频率分别为50.3%,30.3%和19.4%,而在我们入选的524例对照组中的分布频率为57.7%,31.2%和11.1%,研究发现血管紧张素转换酶(ACE)基因I/D多态可能是中国北方汉族人群冠心病发病的独立危险因素(P0.05);利用多元回归分析发现,在调整了冠心病的其他危险因素后,血管紧张素转换酶(ACE)基因I/D多态的变化仍然是中国北方汉族人群冠心病发病一个独立危险因素,可以预测中国北方汉族人群冠心病的发生。结论:在中国北方汉族人群中,血管紧张素转换酶(ACE)基因I/D多态可能是冠心病发病的独立危险因素,在临床上可以早期预判冠心病的发生。     

内蒙古地区达斡尔族血管紧张素转换酶基因多态性分布

目的:研究内蒙古地区达斡尔族血管紧张素转换酶基因(ACE)多态性分布。方法:采用聚合酶链反应检测198例北方汉族和198例达斡尔族中血管紧张素转换酶基因插入/缺失(I/D)多态性分布。结果:ACE基因多态性,达斡尔族人群ID、DD基因频率高于北方汉族,II基因频率低于北方汉族,二组间比较均存在明显差异(P<0.05)。结论:北方汉族与达斡尔族间ACE基因多态性和等位基因频率分布存在差异。     

ACE2基因多态性与高血压患者血压昼夜节律变化相关性研究

目的:研究血管紧张素转换酶2(ACE2)基因多态性与高血压患者血压昼夜节律变化的关系.方法:选择符合入选标准的高血压患者336例,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法,进行ACE2基因分型.根据血压昼夜节律变化,将高血压患者分为勺型与非勺型两组.分析基因型是否为非勺型血压的危险因素.结果:男性勺型组与非勺型组ACE2基因型多态性的分布存在显著差异,勺型组以G等位基因携带者为主.结论:ACE2基因多态性与男性高血压患者血压昼夜节律相关,携带G等位基因的患者可能更易发生夜间血压升高.     

睡眠中间歇低氧伴高血压患者与不同血管紧张素转换酶基因型关系的研究

目的探讨睡眠中间歇低氧-阻塞性睡眠呼吸暂停低通气综合征(OSAHS)伴高血压患者与血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性的关系。方法采用聚合酶链反应技术对2009年1月至2009年12月沈阳医学院奉天医院经多导睡眠监测(PSG)诊断为OSAHS且伴高血压的51例患者(试验组)及60例健康人进行ACE基因型检测,分析ACE基因型(ID组、II组及DD组)与OSAHS伴高血压患者之间关系。结果与对照组相比,试验组DD基因型显著高于II和ID基因型,等位基因频率D显著高于I(P<0.01),收缩压、舒张压、呼吸暂停低通气指数(AHI)水平显著高于对照组(P<0.01),夜间平均血氧饱和度(平均SaO2)显著低于对照组(P<0.01)。试验组中DD基因型频率显著升高(P<0.01),与ID、II基因型对比,收缩压及AHI均显著升高(P<0.05,P<0.01),平均SaO2显著低于对照组(P<0.05),男患多见(P<0.01)。随AHI增加,D等位基因表达增高,收缩压显著升高,平均SaO2显著降低。结论OSAHS伴高血压患者与ACE基因DD基因型相关,D等位基因可能为易感基因。OSAHS是高血压的独立危险因素,OSAHS越重,血压越高,且男性多发。     

优秀赛艇运动员ACE基因I/D多态性与耐力表型的关联研究

血管紧张素转换酶(ACE)基因多态性与人类耐力表型相关。本研究采用cross-sectional方法研究35名赛艇运动员ACE基因I/D多态性与耐力表型指标最大摄氧量(VO_2max)、相对最大摄氧量(VO_2max/kg),肺活量,肺活量/体重之间的差异。研究结果表明,赛艇运动员ACE基因频率经卡方检验符合Hardy-Weinberg遗传平衡定律,Ⅰ等位基因频率为67.2%,D等位基因频率为32.8%,基因型频率分别为Ⅱ型为42.8%,ID型为48.6%,DD型为8.6%,IDⅡDD型,组间卡方检验有显著性差异(p0.05)。ID与DD基因型之间VO_2max、肺活量/体重均存在显著性差异(p0.05),而其他基因型之间的指标比较无显著性差异。赛艇运动员ACE基因I/D多态性与耐力表型有关,Ⅰ等位基因表达高于D等位基因,更倾向于Ⅱ和ID型。     

ACE基因多态性与高血压肾脏损害及PAI-1的关系

为探讨血管紧张素转换酶（ACE）基因多态性与高血压肾损害和纤溶酶原激活物抑制物-1（PAI-1）的关系,应用聚合酶链反应（PCR）检测96例正常人、67例高血压无肾脏损害患者和70例高血压伴肾损害患者的ACE基因型,采用ELISA法检测血浆PAI-1。ACE基因I/D多态性与高血压病无明显相关,但高血压肾损害患者DD基因型频率及D等位基因频率显著高于对照组和高血压无肾脏损害组,χ2值分别为6.8589、5.6162 和5.9085、5372。血浆PAI-1在DD型、ID型、II型高血压患者之间亦有显著性差异（P＜0.05）。ACE基因DD型可能是高血压肾损害的危险因素;ACE基因多态性与血浆PAI-1水平相关。 Abstract:The work is to explore the relationship between the polymorphism of angiotensin converting enzyme(ACE) gene and hypertensive kidney lesion/PAI-1 in hypertension patients.ACE genotyping with polymorase chain reaction (PCR) was performed in 96 unrelated healthy controls,67 hypertensives without kidney lesion and 70 hypertensives complicated with kidney lesion.The plasma PAI-1 were determined with ELISA.No significant differences could be detected between ACE gene I/D polymorphism and hypertension.However,the frequencies of DD genotype and deletion allele among the hypertensives complicated with kidney lesion were higher than those among the healthy controls and those among the hypertensives without kidney lesion."χ2" values were 6.8589,5.6162 and 5.9085,5.372 respectively.The plasma PAI-1 level showed significant differences among DD genotype,ID genotype and II genotype(P＜0.05).The DD genotype of ACE gene may be a risk for hypertensive kidney lesion.The plasma PAI-1 level is associated with ACE gene polymorphism.     

血管紧张素转换酶基因多态性与2型糖尿病发病的相关性研究

目的:探讨血管紧张素转换酶基因(ACE)多态性与其血清水平及2型糖尿病(T2D)发生的相关性.方法:应用聚合酶链反应检测T2D患者287例和正常对照组307例健康人的ACE基因Alu重复序列的插入/缺失(I/D)多态性,采用全自动生化分析仪检测ACE活性及血脂水平,采用SPSS11.0软件包统计分析基因型分布和等位基因频率与其活性、血脂水平及T2D的相关性.结果:ACE I/D多态性在T2D组(DD:13.36%、ID:45.93%、Ⅱ:40.72%)与对照组(DD:13.24%、ID:43.90%、Ⅱ:42.86%)的基因频率无显著性差异(P0.05).T2D组ACE各基因型之间ACE活性有显著性差异(P<0.01).T2D各基因型的血脂水平分析显示Ⅱ型与DD型之间HDL有显著性差异(P<0.05).结论:ACE基因DD型和D等位基因与ACE活性显著相关,但ACE I/D多态性不是T2DM发生的危险因素且无关,DD型与高HDL水平相关.     

汉族人群中血管紧张素转换酶抑制剂所致咳嗽与血管紧张素转换酶基因及缓激肽β2受体基因多态性的关系

目的:探讨汉族人群中血管紧张素转换酶抑制剂(ACEI)所致咳嗽与血管紧张素转换酶(ACE)基因及缓激肽β2受体(BDK-RB2)基因多态性的关系。方法:应用聚合酶链反应(PCR)方法,检测汉族人群中151例由于服用ACEI引起的咳嗽患者及151例未发生咳嗽的患者的ACE I/D及BDKRB2 C/T的多态性,并采用紫外法检测ACE活性。结果:发现ACE基因分布在咳嗽组中II型为47.0%,ID型为42.4%,DD型为10.6%;无咳嗽组分别为39.7%、47.0%、13.3%,两组相比其差异具有统计学意义(P<0.01);BDKRB2基因分布在咳嗽组中CC型为21.3%,CT型为50.0%,TT型为28.7%,无咳嗽组分别为22.5%、47.7%、29.8%,两组相比其差异无统计学意义(P>0.05);咳嗽组ACE活性水平为([28.3±10.1)U/L]明显低于无咳嗽组([40.2±9.4)U/L],两组相比其差异具有统计学意义(P<0.01)。结论:汉族人群中ACEI所致咳嗽与ACE基因多态性及血清ACE水平有关,BDKRB2 C/T与咳嗽间未发现有统计学意义的关联。     

ACE2及其特殊功能

血管紧张素转换酶2（angiotensin—converting enzyme 2,ACE2）是新发现的与血管紧张素转换酶（ACE）相关的羧肽酶,在肾素-血管紧张素系统（rennin-angiotensin system,RAS）中ACE2可以使AngⅡ转换为Ang1-7,从而产生与血管紧张素Ⅱ相反的效应,同时ACE2还可使Ang I转换为Ang1-9。研究发现：ACE2与高血压、SARS以及肾脏、生殖等系统的疾病有着密切的关系。     

一组中国河南汉族群体血管紧张素转换酶基因多态性与血清酶活性研究

为研究中国汉族群体血管紧张素转换酶(angiotensin-1 converting enzyme,ACE)活性、基因多态性分布及相互关系,用分光光度法检测496例汉族个体血清酶活性,PCR后的限制性酶切片段长度多态性(PCR-RFLP)法检测血管紧张素转换酶基因启动子区A-5466C、T-3892C、A-240T及编码区T1237C、G2215A、G2350A共6个SNP位点,以及第16内含子的A／u片段插入／缺失(I／D)和3’端4656(CT)。共8个多态位点的分布,同时用最大期望值(expectationmaximization,EM)算法估计基因连锁不平衡状态和单倍型结构。结果发现,上述8个多态存在于常见的9个单倍型中,其中两种最常见的单倍型为A(A-T-A-T-G-I-A-3)和B(C-C-T-C-A-D-G-2),A和B在每个位点都不相同。最大简约法分析提示本群体可被分为3个进化簇,Ⅲ簇最有可能由Ⅰ簇和Ⅱ簇产生。ACE基因各位点多态性在个体中的分布与血清中ACE活性有关,组成单倍型A的各等位位点与血清中ACE低活性有关,单倍型B的各等位位点与血清中ACE高活性有关。研究结果提示,本群体中ACE基因存在连锁不平衡,有两种主要的单倍型,单倍型B可能与导致ACE升高的数量性状(QTL)关联,但确定具体的数量性状位点还需绘制精细物理图谱。     

G蛋白β亚单位C825T基因多态性与原发性高血压的相关性研究

分析大规模日本人群的G蛋白β亚单位基因（GNB3,C825T-Gprotein β3 subunit C825T）多态性与原发性高血压病（essential hypertension,EH）的关系。采集日本同一个地区健康体检人群为研究对象,共4,830例,其中高血压组（HT：2,092例）,正常血压组（NT：2,738例）。对体检对象做：体重指数（BMI）、吸烟,饮酒等环境因素和血浆胆固醇、甘油三酯等血液生化指标的测量。并用Taqman—PCR化学分析方法对GNB3基因的C825T多态性进行分型检测。GNB3基因的C825T多态性符合Hardy—Weinberg平衡遗传规律。在HT与NT之间,CC、CT、TT遗传表型的频率为NT：24．8％,47．8％和27．4％;HT：22．9％,51．7％和25．4％。C等位基因频率分别为NT：48．72％及HT：48．78％;C825T基因型在HT及NT组之间有显著性差异,基因型频率CC／CT＋TT：P=0．027;OR：1．169;CI95％：1．019～1．341;等位基因频率在两组之间也有统计学差异。C,T：P=0．001;OR：1．154;CI95％：1．064—1．252。CT＋TT基因型携带者发生EH病的危险性为CC基因型携带者的1．169倍（OR）。GNB3基因的C825T的T等位基因EH发病危险是C的1．154倍。GNB3的C825T基因多态性可能是日本人群EH的一个候选基因。     

Association between the G-protein β3 subunit C825T polymorphism with essential hypertension: a meta-analysis in Han Chinese population

We aimed to evaluate the contribution of the G-protein β3 subunit C825T (GNB3-C825T) polymorphism to essential hypertension (EH) in Han Chinese population by performing meta-analysis. A meta-analysis was performed in 12 case-control genetic association studies including 3,020 hypertension patients and 2,790 controls from MEDLINE (PubMed) and the China National Knowledge Infrastructure platforms. The STATA 10.0 software was used in analysis. Overall, there was no significant association between the GNB3-C825T polymorphism and EH in neither additive [TT vs. CC: OR (95 % CI) = 1.11 (0.74-1.69), P = 0.61; TC vs. CC: OR (95 % CI) = 1.08 (0.89-1.31), P = 0.42], nor dominant [TT + TC vs. CC: OR (95 % CI) = 1.11 (0.86-1.42), P = 0.43] and nor recessive [TT vs. TC + CC: OR (95 % CI) = 1.04 (0.75-1.44), P = 0.81] genetic models. Although further subgroup analysis found statistically significant results [T vs. C: OR (95 % CI) = 1.50 (1.05-2.15), P = 0.03] in the southern population, but after exclusion one particular study, the significant association was disappeared. No significant result was found in the northern Han Chinese population. There was no significant association identified between GNB3-C825T polymorphism and EH in Han Chinese population. Further larger sample and well-designed studies are needed to assess the genetic association particularly in the southern Han Chinese population.     

Association of GNB3 gene C825T polymorphism with coronary heart disease

The C825T polymorphism in the gene encoding the G protein beta 3 subunit (GNB3) causes enhanced G protein activation and the increased in vitro cell proliferation. We investigated the association of gene GNB3 C825T polymorphism with coronary artery disease (CAD) in the Russian population. A total of 313 patients with CAD diagnosed on the basis of clinical studies and coronary angyography were examined. The control group included 132 individuals that lacked clinical CAD symptoms and had matching profile of coronary artery disease risk factors. Blood pressure was measured using standard protocols. Increased levels of diastolic and systolic pressure was observed in both groups. The allele and genotype frequencies of this polimorphic marker were significantly higher in the CAD patients than in control. We found that the frequency of allele C and gen-. otype CC was significantly higher in the CAD patients (OR = 1.55; P = 0.0079; OR = 1.63; P = 0.0215, respectively), which suggests higher risk of this pathology in carriers of allele C and genotype CC. Thus, in the Russian population coronary artery disease is associated with GNB3 allele C and genotype CC.     

Association of G-protein beta-3 subunit gene (GNB3) T825 allele with Type II diabetes

To date, the human G-protein beta 3 subunit (GNB3) gene and some of its variants represent some of the best examples of genetic influences that are involved in the determination of hypertension and obesity, which make it a sensible candidate gene for type 2 diabetes. To assess the influence of GNB3 in type II diabetes mellitus (NIDDM), we carried out a retrospective, case-control study of variant GNB3 825C>T for putative correlations with NIDDM amongst nationals from the United Arab Emirates (Emirati) - an ethnic group characterized by no alcohol intake and no cigarette smoking. We investigated a sample population of 510 Emirati (257 men, 253 women) comprising two groups - 254 controls and 256 patients with clinical diagnoses of type 2 diabetes (cases). The GNB3 C825T dimorphism showed an association with NIDDM Chi2 =22.5, 2 df, P<0.001). Further analysis revealed that the GNB3 T/T 825 genotype was positively associated with NIDDM (Yates corrected Chi2=20.6, 2 df, P<0.001; odds ratio of 2.44 with a 95% confidence interval of 1.64 - 3.63) compared to pooled CC/CT genotypes. Our data shows that GNB3 T825 allele may be involved in the pathogenesis of DM through a pathway that is different from the one implicated in obesity.     

Case-control study on association of peroxisome proliferator-activated receptor-δ and SNP-SNP interactions with essential hypertension in Chinese Han population

The aim of this study was to investigate the association of peroxisome proliferator-activated receptor-δ (PPAR-δ) and additional SNP-SNP interaction with essential hypertension (EH) in Chinese Han population. A total of 1248 subjects (625 males, 623 females), including 620 EH patients and 628 normotension subjects, were included in the study. The mean age was 51.2?±?15.1 years old. Logistic regression model was used to examine the association between four SNP and EH; odds ratio (OR) and 95 % confident interval (95 %CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze SNP-SNP interaction. EH risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with TT (TC?+?CC versus TT, adjusted OR (95 %CI)?=?0.61 (0.49–0.78)). In addition, we also found a significant association between rs9794 and EH; EH risk was also significantly lower in carriers of G allele of the rs9794 polymorphism than those with CC (CG?+?GG versus CC, adjusted OR (95 %CI)?=?0.65 (0.53–0.83)). We also found a potential SNP-SNP interaction between rs2016520 and rs9794; subjects with TC or CC of rs2016520 and CG or GG of rs9794 genotype have the lowest EH risk, compared to subjects with TT of rs2016520 and CC of rs9794 genotype; OR (95 %CI) was 0.32 (0.23–0.62) after covariate adjustment. Our results support an important association between rs2016520 and rs9794 minor allele of PPAR-δ and decreased risk of EH and additional interaction between rs2016520 and rs9794.     

Interactions among Candidate Genes Selected by Meta-Analyses Resulting in Higher Risk of Ischemic Stroke in a Chinese Population

Ischemic stroke (IS) is a multifactorial disorder caused by both genetic and environmental factors. The combined effects of multiple susceptibility genes might result in a higher risk for IS than a single gene. Therefore, we investigated whether interactions among multiple susceptibility genes were associated with an increased risk of IS by evaluating gene polymorphisms identified in previous meta-analyses, including methylenetetrahydrofolate reductase (MTHFR) C677T, beta fibrinogen (FGB, β-FG) A455G and T148C, apolipoprotein E (APOE) ε2–4, angiotensin-converting enzyme (ACE) insertion/deletion (I/D), and endothelial nitric oxide synthase (eNOS) G894T. In order to examine these interactions, 712 patients with IS and 774 controls in a Chinese Han population were genotyped using the SNaPshot method, and multifactor dimensionality reduction analysis was used to detect potential interactions among the candidate genes. The results of this study found that ACE I/D and β-FG T148C were significant synergistic contributors to IS. In particular, the ACE DD + β-FG 148CC, ACE DD + β-FG 148CT, and ACE ID + β-FG 148CC genotype combinations resulted in higher risk of IS. After adjusting for potential confounding IS risk factors (age, gender, family history of IS, hypertension history and history of diabetes mellitus) using a logistic analysis, a significant correlation between the genotype combinations and IS patients persisted (overall stroke: adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.22–2.02, P < 0.001, large artery atherosclerosis subtype: adjusted OR = 1.50, 95% CI: 1.08–2.07, P = 0.016, small-artery occlusion subtype: adjusted OR = 2.04, 95% CI: 1.43–2.91, P < 0.001). The results of this study indicate that the ACE I/D and β-FG T148C combination may result in significantly higher risk of IS in this Chinese population.     

ACE I/D polymorphism in Alzheimer’s disease

Angiotensin-converting enzyme (ACE) has been reported to show altered activity in patients with neurological diseases. The recent studies found that a 287 bp insertion/deletion (I/D) polymorphism of the ACE gene may be associated with susceptibility to Alzheimer’s disease (AD) but the results have been heterogenous between studies in Europe. In the present study we examined for the first time the association of ACE I/D polymorphism along with APOE genotype in 70 sporadic AD and 126 control subjects in Slovak Caucasians (Central Europe). An increased risk for AD was observed in subjects with at least one APOE*E4 allele (OR=3.99, 95% CI=1.97–8.08). No significant differences for the genotype distribution or the allele frequency were revealed comparing controls and patients for ACE gene. Gene-gene interaction analysis showed increase of the risk to develop AD in subjects carrying both the ACE DD genotype and the APOE*E4 allele (OR=10.32, 95% C.I. 2.67–39.81).     

Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression

The G protein beta3 subunit (GNB3) 825T allele is predictive of enhanced Gi protein activation. Studying the influence of C825T allele status on cellular in vitro immune responses towards recall antigens and interleukin-2 stimulation we observed a 2-4-fold, significantly increased proliferation in homozygous 825T (TT) vs. C825 allele (CC) carriers. Furthermore, lymphocyte chemotaxis and CD4(+) T cell counts of individuals with TT+TC genotypes were significantly enhanced compared to the CC genotype. In summary, it appears that C825T allele status is highly predictive of immunocompetence and could be a candidate gene in disorders associated with inadequate immune response.