血管紧张素I转换酶基因I／D多态性与特发性肺纤维化的相关性研究

目的探讨血管紧张素I转换酶（ACE）基因I／D多态性在特发性肺纤维化（IPF）发病中的作用。方法应用PCR技术检测42例IPF患者（IFP组）和90例健康查体者（对照组）ACE基因I／D多态性,并分析不同基因型和等位基因者IPF发病危险性。结果IPF组DD基因型和D等位基因频率均显著高于对照组（P〈0．05）;与Ⅱ基因型比较,携带DD型和D等位基因个体发生IPF的风险分别增加2．97倍（95％CI为1．13—7．73）和1．96倍（95％CI为1．16—3．32）,P均〈0．05。结论ACE基因I／D多态性与IPF发病有关,DD基因型和D等位基因可能增加IPF的患病风险。     

ACE基因I／D多态性与缺血性脑卒中的关系

为了解血管紧张素转换酶（ACE）基因I／D多态性与中国人群缺血性脑卒中之间的关系,利用PCR和分子杂交技术对北京地区294例缺血性脑卒中患者及280例非卒中者的ACE基因I／D多态性进行了检测和分析。结果表明,I／D多态性在两组人群中的分布均符合Hardy-Weinberg遗传平衡定律,但该位点的基因型频率及等位基因频率在两组人群中分布无差异,与英国人群相比则有显著差异。提示ACE基因I／D多态性不是中国人群缺血性脑卒中发病的遗传学危险因素。     

血管紧张素转换酶基因多态性与不同性别慢性心力衰竭患者发病的相关性研究

目的探讨我国南方汉族人群中,血管紧张素转换酶(ACE)基因多态性与不同性别慢性心力衰竭(CHF)发病的关系。方法应用聚合酶链反应技术测定82例男性和48例女性CHF患者(试验组),以及89名男性和41名女性健康者(对照组)的ACE基因插入/缺失(I/D)多态性,并进行统计学比较。结果共检测出3种ACE基因型,分别为II型、ID型和DD型。试验组患者DD基因型及D等位基因均高于同性别对照组;与非DD型者相比,男性DD型者发生CHF的相对风险率为1.918;女性DD型者发生CHF的相对风险率为2.727。结论ACE基因I/D多态性与中国南方汉族人群不同性别CHF的发生均相关,D等位基因可能是该地区CHF发病的遗传危险因素。与男性相比,DD基因型女性罹患CHF的可能性更大。     

CD40基因单核苷酸多态性及单倍型与缺血性脑卒中的相关性研究

目的研究CD40基因单核苷酸多态性及其单倍型与缺血性脑卒中易感性之间的关系;同时分析CD40基因型及血清水平与缺血性脑卒中的相关性。方法选择缺血性脑卒中患者202例(脑卒中组),健康体检者199例(对照组),应用单碱基延伸的PCR技术和DNA测序法对CD40基因rs1883832C/T、rs1569723A/C和rs4810485G/T单核苷酸多态性进行基因分型,同时采用ELISA法检测血清CD40水平。结果脑卒中组与对照组CD40基因rs1883832C/T位点基因型和等位基因频率比较,差异有统计学意义(P<0.01)。等位基因频率的相对风险分析发现,rs1883832T等位基因携带者患缺血性脑卒中的风险是C等位基因的1.557倍(P=0.002);携带rs1883832T等位基因的缺血性脑卒中患者血清CD40水平显著高于不携带者(P<0.05)。联合基因型分析发现,脑卒中组T-C-T单倍型携带者较对照组明显增加了发病风险(P=0.033)。结论 CD40基因rs1883832C/T多态性和T-C-T单倍型与缺血性脑卒中的发病具有相关性,其中T等位基因可能是缺血性脑卒中的遗传易感基因,携带T等位基因的个体可能通过促进CD40的高度表达进而增加了缺血性脑卒中的发病风险。     

血管紧张素转化酶基因多态性与中国人群消化道肿瘤易感性的Meta分析

目的通过Meta分析评估血管紧张素转化酶(ACE)基因I/D多态性与中国人群消化道肿瘤发病的相关性。方法通过计算机文献检索中国生物医学文献数据库(CBM)和Pub Med数据库,并结合文献追溯的方法,收集所有关于ACE基因多态性与消化道肿瘤易感性的病例对照研究或队列研究。以消化道肿瘤组与对照组人群基因型分布的OR值为效应指标,各资料间进行一致性检验,以确定采用固定或随机效应模型进行合并分析。发表偏倚用漏斗图和Egger线性回归检验来评估。结果纳入在国内外发表的相关文献6篇,Meta分析结果表明:D等位基因相对于I等位基因合并OR值(95%CI)为1.32(0.46~3.79)(P>0.05),DD基因型相对于DI/II基因型合并OR值(95%CI)为0.89(0.39~2.01)(P>0.05),DD/DI基因型相对于Ⅱ基因型合并OR值(95%CI)为1.08(0.89~1.31)(P>0.05),DD基因型相对于Ⅱ基因型合并OR值(95%CI)为0.86(0.43~1.75)(P>0.05),DI基因型相对于II基因型合并OR值(95%CI)为1.02(0.74~1.40)(P>0.05),差异均无统计学意义。结论中国人群ACE基因I/D多态性与中国人群消化道肿瘤易感性无明显关联。     

ATP结合盒转运体A1基因R219K多态性与中国人缺血性卒中风险:汇总分析

目的 探讨ATP结合盒转运体A1(ATP-binding cassette transporter A1,ABCA1)基因R219K多态性与中国人缺血性卒中的相关性.方法 采用全面的文献检索收集2013年5月以前发表的中国人ABCA1基因R219K多态性与缺血性卒中相关性的病例对照研究.采用Stata 11.0软件包进行汇总分析.采用优势比(odds ratio,OR)及其95％可信区间(confidence interval,CI)评价基因多态性与缺血性卒中的关联强度.结果 共10项研究符合条件纳入分析,包括病例组1 619例,对照组1 907例,入选文献无明显偏倚.汇总分析显示,RK+KK基因型携带者缺血性卒中风险较RR基因型携带者显著性降低8％(OR0.92,95％ CI 0.88～0.96;P =0.000);KK基因型携带者的缺血性卒中风险较RR基因型携带者显著性降低36％(OR 0.64,95％ CI 0.44～0.94;P=0.02);RK基因型携带者的缺血性卒中风险较RR基因型携带者显著性降低19％(OR0.81,95％ CI 0.69～0.95;P=0.009);K等位基因携带者的缺血性卒中风险较R等位基因携带者显著性降低17％(OR 0.83,95％ CI 0.69～0.99;P=0.036).结论 ABCA1基因R219K多态性与中国人缺血性卒中易感性相关,K等位基因可能是中国人缺血性卒中的遗传保护性因素.     

血管紧张素转换酶基因多态性与冠脉病变严重程度的相关性研究

目的探讨血管紧张素转换酶(ACE)基因I/D多态性与冠心病及冠脉病变严重程度的关系.方法对122例冠心病患者进行冠状动脉造影,判定冠脉病变支数(狭窄程度≥75%)和危险记分.用聚合酶链式反应(PCR)技术检测病例组和80例健康人群ACE基因多态性.结果ACE基因型分布和等位基因频率在病例组和对照组间差异有显著性,病例组DD基因型(38.5%)和D等位基因频率(55%)显著高于对照组(13.7%,41%;P＜0.05).冠脉病变支数和危险记分在ACE基因型间差异无显著性(P＞0.05).结论ACE基因多态性中DD型和D等位基因是冠心病发病的独立危险因素,但与冠脉病变严重程度不相关.     

血管紧张素转换酶基因多态性与非杓型高血压的关系

目的研究血管紧张素转换酶 ( ACE)基因插入 /缺失 ( I/ D)多态性与非杓型高血压 ( EH)的关系。方法　 1应用聚合酶链反应 ( PCR)方法扩增 5 0例正常人、99例高血压患者的 ACE基因上 2 87bp片段 ,根据插入 ( I)或 /缺失( D)来判断其多态性。 2高血压患者行 2 4h动态血压监测 ( ABPM) ,根据 ABPM结果分为杓型 EH组和非杓型 EH组。结果　 1非杓型组与健康对照组相比 ,其 D等位基因及 DD基因型显著升高。 2非杓型组与杓型组相比 ,其 D等位基因及 DD基因型显著升高。3杓型组与健康对照组相比 ,ACE基因型和等位基因频率无显著性差异。结论　ACE基因多态性与非杓型高血压有关联性 ,DD基因型提示可能与高血压昼夜节律改变有关     

血管紧张素转换酶基因多态性与心肌梗塞发病相关性研究

对104例正常人和97例心肌梗塞患者用PCR方法检测其ACE基因型及血清ACE水平。ACE基因多态性分为DD、ID、II型。结果表明等位基因频率D=0.56,I=0.44,三种基因型之间血脂、脂蛋白、血糖、胰岛素、BMI等无差异。DD、ID、II型ACE水平分别为38.35±10.24u、30.74±9.6u、29.03±5.26u(P<0.01)。ACE DD型与心肌梗塞相关,D等位基因频率梗塞组高于对照组,OR值为1.55(P=0.003)。在低危人群中DD基因型频率梗塞组高于对照组,DD基因型与梗塞的相关性增高,OR值由1.55增高为1.65、1.69。有冠心病家族史者其DD基因型频率高于无冠心病家族史者,OR为1.87(P=0.02)。因此,ACE I/D基因多态性与血清ACE水平相关,ACE DD是冠心病、心肌梗塞的潜在危险因素,尤其对于低危人群。     

ACE基因、AT1R基因多态性与2型糖尿病肾病的关系

目的研究血管紧张素I转化酶(ACE)基因/D多态及血管紧张素受体1型(AT1R)A1166C多态性与中国汉族人2型糖尿病肾病(DN)的关系。方法运用聚合酶链反应(PCR)和PCR/DdeI酶切技术,检测93例DN患者(DN组)与94例2型糖尿病患者(DM组)ACE基因及AT1R基因多态基因型。结果DN组ACE基因DD基因型频率(34.4%)、D型等位基因频率(54.3%)较DM组(19.1%,40.4%)均升高(P<0.05,<0.01);两组间AT1R基因A1166C多态基因型频率和等位基因频率分布均无差异(P>0.05);ACE和AT1R基因多态与DN的分层分析显示,同时携带ACE纯合子缺失基因型(DD)和AT1R突变基因型(AC+CC)者发生DN的危险较大,OR值为8.569。结论ACE基因/D多态性与2型DM并发DN有关,携带DD基因型和D型等位基因的2型DM患者是DN的易感人群。ATlR基因A1166C多态性虽与我国汉族人2型DM并发DN无关,但AT1R与ACE基因多态存在协同效应,携带AC+CC与DD基因型的个体有更高的患DN风险。     

The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.     

脑出血患者载脂蛋白E和血管紧张素转换酶的基因多态性分析

目的探讨载脂蛋白E（apoliportein E,ApoE）和血管紧张素转换酶（angiotensin converting enzyme,ACE）基因多态性与脑出血的关系。方法应用聚合酶链反应-限制性片断长度多态性技术检测80例脑出血患者和90名健康对照者的ApoE和ACE基因型和等位基因。并运用Logis-tic回归分析ApoE和ACE基因多态性与脑出血的相关性。结果脑出血组ApoE的基因型频率和等位基因频率与正常对照组比较,差异均无统计学意义,P〉0.05;ACE的DD基因型频率为35.0%,D等位基因频率为51.9%,明显高于正常对照组的15.6%、38.9%,均P〈0.05;Logistic回归分析显示,ACE的DD基因型的患者患脑出血的OR值为2.923（95%CI：1.406-6.079）;同时携带ACE基因DD型和ApoE E3/4基因型的患者患脑出血的OR值为3.428（95%CI：1.045-11.237）。结论ACE基因插入/缺失多态性可能是脑出血发病的独立遗传因素;与ApoE基因多态性间具有协同致脑出血的作用。     

老年脑卒中患者血浆ACE水平及其基因多态性的研究

血管紧张素转换酶(ACE)在肾素-血管紧张素-醛固酮系统(RASS)和激肽释放内原-激肽系统(KKS)中发挥着重要的作用。近年研究发现,ACE通过不同的遗传机制在心脑血管疾病的发生发展中发挥作用,其多态性决定了血浆和细胞内ACE浓度,是研究各类心脑血管疾病遗传易感性的候选基因,本文通     

血管紧张素转换酶基因多态性与老年脑卒中的相关性

目的探讨血管紧张素转换酶(ACE)基因多态性与老年脑卒中的相关性。方法选择186例脑卒中患者(脑卒中组)分为脑血栓组(126例)和脑出血组(60例),另选75例同期住院的非脑卒中患者作为对照组。采用PCR-RFLP技术,检测ACE第16内含子中长度为287bp碱基片段的插入/缺失情况,并分别测定其基因型频率和等位基因频率。结果脑卒中组D等位基因频率为41.9%,对照组为31.3%,两组比较差异有显著性意义(P<0.05);脑卒中组DD型基因频率为21.5%,对照组为9.3%,两组比较差异有显著性意义(P<0.05);脑血栓组和脑出血组D等位基因和DD型基因与对照组比较差异有显著性意义(P<0.05)。结论ACE基因多态性与老年人脑卒中相关,其DD型基因和D等位基因是老年脑卒中的危险因素。     

ACE genotype, risk and causal relationship to stroke: Implications for treatment

Opinion statement The angiotensin-converting enzyme (ACE) catalyzes the formation of angiotensin II and the breakdown of bradykinin into inactive products. The insertion/deletion (I/D) polymorphism affects the activity of the enzyme, with the DD genotype being responsible for the highest activity of the enzyme. Meta-analysis of 11 studies including white persons showed that the DD genotype was a risk factor for ischemic stroke. No such correlation was found in an Asian population. Studies on different etiologies or intermediate phenotypes of ischemic stroke did not bring univocal results. There are still no convincing data on whether the I/D polymorphism of the ACE gene is a risk factor for spontaneous intracerebral hemorrhage and intracranial aneurysms, ruptured or unruptured. Several pharmacogenetic studies analyzed the influence of the ACE I/D polymorphism on the response to acute stroke therapy (thrombolysis) or prevention strategies (lifestyle modification and treatment of vascular risk factors). Presently, however, there is no consensus on whether the efficacy of these therapies is affected by the ACE gene I/D polymorphism.     

血管紧张素转换酶和血管紧张素受体基因多态性与冠心病的关系

目的　探讨深圳地区冠心病 (CAD)与血管紧张素转换酶 (ACE)基因与血管紧张素 的 1型受体 (AT1R)基因多态性的关系。方法　分别采用 PCR及 PCR- Afl II酶切法 ,检测 89例 CAD患者和 14 8例健康对照的 ACE和AT1R基因型。结果　 CAD组与对照组比较 ,ACE DD基因型频率 (2 4 .7%比 8.1% ,P<0 .0 1)及 D型等位基因频率 (4 4 .4 %比 33.4 % ,P<0 .0 5 )均为升高。 CAD组与对照组 AT1R基因型频率分布无显著性差异 (P>0 .0 5 )。携带 AT1R C等位基因的个体患 CAD的风险与其同时携带 ACE DD基因型无关 (P>0 .0 5 )。结论　深圳地区CAD的发生和发展可能与 ACE基因 I/ D多态性有关 ,而与 AT1R基因 A116 6 C多态性无关     

Interaction of the ACE D allele and the GNB3 825T allele in myocardial infarction

In polygenetic disorders, such as ischemic heart disease, the investigation of gene-gene interactions rather than determination of single gene effects is crucial to better understand the contribution of genetic factors. The 825T allele of the G-protein ss(3)-subunit gene (GNB3) associated with enhanced G-protein signaling is a candidate to interact with the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism to increase the risk for myocardial infarction (MI). The ACE D:/I variant affects the renin-angiotensin system hormones that activate G-protein-coupled receptors. Genotyping at the ACE and GNB3 loci was performed on 585 patients with coronary artery disease with (n=270) or without (n=315) previous MI. Logistic regression analysis demonstrated a significant interaction between the ACE D: allele and the GNB3 825T allele (P<0.001). The odds ratio for MI, associated with the 825T allele, was not increased in the presence of the ACE II genotype (OR 0.5; P=0.09) but was significantly higher in 825T allele carriers with the ACE DI genotype (OR 1.9; P=0.01) and further increased in individuals with the ACE DD genotype (OR 2.4; P=0.02). The highest odds ratio was found in homozygous 825T allele carriers with the ACE DD genotype (OR 7.5; P=0.006). Our data suggest a significant interaction of the GNB3 825T allele with the ACE D allele in MI. These hypothesis-generating data may justify larger prospective studies.     

Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction

A synergistic interaction between the insertion/deletion (I/D) polymorphism within the angiotensin-converting enzyme (ACE) gene and an A/C transversion at nucleotide position 1166 within the angiotensin II sub-type 1 receptor (AT1R) gene on risk of myocardial infarction has been reported. The risk associated with the ACE DD genotype increased with the number of AT1R C alleles present. To investigate this further, ACE I/D and AT1R A1166C genotypes were determined in 541 cases recruited at the time of infarction and 507 population-based controls. There was no difference in either the genotype distribution or allele frequencies between cases and controls for either the ACE polymorphism (P=0.48 and 0.35 respectively) or the AT1R polymorphism (P=0.35 and 0.21 respectively). Odds ratios for risk of MI associated with the ACE DD and AT1R CC genotypes were 1.09 (95% CI, 0.82-1.45) and 1.06 (0.67-1.68) respectively. 3.1% of cases versus 3.6% of controls were homozygous for both the D and C alleles (P=0.71). There was no increase in risk associated with the DD genotype in the presence of either one or two AT1R C alleles in the whole cohorts (OR 0.99, 95% CI 0.65-1.51 and 0.76, 95% CI 0.30-1.88, respectively) nor in sub-groups defined by specific risk factors. In conclusion, no evidence was found to support any interaction between the ACE gene I/D polymorphism and the ATIR gene A1166C transversion in determining the risk of myocardial infarction in the population studied.