ACE基因多态性与老年人原发性高血压的关系

目的 探讨血管紧张素Ⅰ转换酶（ACE）基因多态性与老年人原发性高血压（EH）的相关性。方法 采用一步PCR3条引物法,对287例老年EH（高血压组）和301例正常老年人（对照组）进行ACE基因I／D多态性分型,并进行基因型及等位基因频率计数,组间采用χ^2检验进行统计学分析。结果 高血压组DD型基因频率及D等位基因频率分别为10．4％和30．5％,对照组分别为9．3％和31．2％,经χ^2检验,2组间无显著差别（P＞0．05）。结论 ACE基因多态性与老年人原发性高血压（EH）无关。一步PCR3条引物法更准确可靠,可减少DD型错判率。     

原发性高血压病患者血管紧张素转换酶的基因多态性分析

目的：采用三条引物法进行血管紧张素转换酶(ACE)基因分型，并与Rigat法进行比较，探讨ACE基因多态性与原发性高血压病(EH)之间的关系。方法：抽取外周血DNA，分别用三条引物法和Rigat法对128例EH患者进行ACE基因分型，并以150例正常人作对照组。结果：Rigat法对DD型的错判率为22．22％。正常血压人群ACE基因DD型、Ⅱ型、ID型分别有10、62、78例，占6．67％、41．33％、52％，Ⅰ和D的等位基因频率是67％、33％；原发性高血压病人群ACE基因DD型、Ⅱ型、ID型分别有14、47、67例，占10．94％、36．72％、52．34％，Ⅰ和D的等位基因频率是63％、37％。结论：ACE基因多态性与原发性高血压有一定关系。     

ACE基因I/D多态性与原发性高血压和高血压性脑出血的关系

目的研究血管紧张素转换酶（ACE）基因插入/缺失（I/D）多态性的分布及其与原发性高血压（EH）、高血压性脑出血（CH）之间的关系。方法采用常规酚—氯仿抽提法提取外周血基因组DNA,PCR检测ACE基因I/D多态性基因型频率及等位基因频率。结果 EH、CH患者及健康对照者ACE基因DD基因型频率分别为17.95%、17.55%、6.45%;D等位基因的分布频率分别是45.51%、45.18%、33.06%。与健康对照比较,EH和CH患者间ACE基因DD基因型频率和D等位基因频率均显著增高（P〈0.05）,但EH和CH患者间无统计学差异。结论 ACE基因DD基因型和D等位基因可能是EH和CH的遗传易感基因。     

性别因素对原发性高血压候选基因研究的影响作用

目的探讨研究样本中的性别因素对原发性高血压（EH）候选基因研究结果的影响。方法应用聚合酶链反应这一分子生物学研究方法,分析EH组患者及正常血压对照组（两组中男性女性人数相等）人群血管紧张素转换酶（ACE）基因插入／缺失（I／D）多态性,进而探讨性别比例对该类研究结论的可能影响。结果男性EH组DD基因型频率显著高于男性对照组（x^2=6．98,P=0．004）,D等位基因频率在男性EH组亦较男性对照组显著增高（x^2=6．87,P=0．009）,而ID和II基因型频率在男性EH组和男性对照组间差异无统计学意义（P〉0．05）。女性EH组与女性对照组比较,各基因型和等位基因频率分布差异均无统计学意义（P〉0．05）;男性EH组中的DD基因型分布比例与女性EH组中的DD基因型分布比例相比有显著统计学意义（x^2=4．06,P=0．044）。此外,EH组中男性DD型者的收缩压及脉压水平均显著高于ID型和II型者（P均〈0．05）,但舒张压在3种基因型间差异无统计学意义（P〉0．05）。同时,EH组II、ID基因型的男性的收缩压、舒张压、脉压差异均无统计学意义（P〉0．05）。女性患者中,各基因型间收缩压、舒张压及脉压的水平差异均无统计学意义（P〉0．05）。结论男性中的DD基因型成员与EH（尤其在收缩压、脉压）的关联可能比男性中的II、ID基因型以及所有的女性更为密切。性别可能作为一个混杂因素,对包括ACE基因I／D多态性在内的诸多EH候选基因与EH的相关性研究的结论产生影响。     

HLA—DRB和ACE基因与肺结核的相关性分析

目的探讨人类白细胞抗原（HL气）-DRB基因和血管紧张素转换酶（ACE）基因多态性与肺结核的相关性。方法采用聚合酶链反应-序列特异性引物法（PCR—SSP）对肺结核组和健康对照组进行HLA-DRB和ACE基因分型。结果肺结核组HLA—DRB1＊15等位基因的频率显著高于对照组（P〈0．05）；复治和耐药肺结核组ACE基因的I／D基因型频率显著高于初治和无耐药组（P〈0．05）。结论HLA—DRB1＊15等位基因及ACE基因的I／D基因型与肺结核密切相关。     

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     

ACE基因(I/D)多态性与家族性原发性高血压的关系

目的:探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与家族性原发性高血压(EH)的关系。方法:采用原位杂交荧光染色脱氧核糖核酸测序法,检测46例有家族史EH患者(有家族史EH组)及64例无家族史的EH患者(无家族史EH组)和43名健康人群(健康对照组)的ACE基因I/D多态性基因型频率及等位基因频率。结果:健康对照组、无家族史EH组及有家族史EH组患者ACE基因DD基因型频率分别是11.6%、32.3%、37.0%;D等位基因的分布频率分别是33.7%、52.3%、57.6%。和健康对照组比,无家族史EH组和有家族史EH组患者ACE基因DD基因型和D等位基因频率均明显升高(P<0.05或<0.01),但无家族史EH组和有家族史EH组患者间无统计学差异(P>0.05)。结论:ACE基因DD基因型和D等位基因可能是原发性高血压患者的遗传易感基因,而无家族史的高血压患者和有家族史的高血压患者两组基因构成比无差别。     

昆明汉族ACE、AT1R基因多态性与2型糖尿病肾病的关系

运用聚合酶链反应（PCR）和PCR／Ddel酶切技术,检测110例DN患者[DN（＋）组]与74例2型糖尿病无肾病患者[DN（-）组]及56例正常对照人群ACE基因及AT,R基因多态性。结果（1）DN（-）组ACE—DD基因型和D等位基因频率与正常对照组比较无显著性差异（P〉0．05）;（2）DN组ACE基因DD基因型频率（56．4％）,D型等位基因频率（70．5％）较DN（-）组（21．6％,46．6％）均升高（P〈0．01）;（3）三组间AT1R基因的A1166C多态基因型频率和等位基因频率分布均无差异（P〉0．05）;（4）联合作用分析同时携带ACE纯合子缺失基因型（DD）和AT,R突变基因型（AC＋CC）者发生DN的危险较大,OR值为5．421。结论昆明地区汉族人ACE基因I／D多态性与2型DN发生有关,携带DD基因型和D型等位基因者是2型DN的易感人群。AT1R基因A1166C多态性与2型DN无关,但携带AC＋CC与DD基因型的个体有更高的患DN风险。     

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。     

血管紧张素转换酶基因多态性与2型糖尿病肾病的相关性

应用PCR技术检测144例2型糖尿病患者（T2DM组）的血管紧张素转换酶（ACE）基因插入/缺失（I／D）多态性,并与67例健康人（对照组）比较,结果两组间ACE等位基因、基因型频率无显著性差异（P〉0．05）;T2DM组伴DN者（80例）DD基因型频率显著高于不伴DN者（64例）（P〈0．05）;DN患者中肾功能不全者DD基因型及D等位基因频率均明显高于肾功能稳定者（P〈0．05）。提示ACE基因I／D多态性与T2DM的易感性无关,与DN的发生、发展密切相关。     

Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects

Inconsistent results have been reported regarding the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and hypertension. Recent studies of population-based samples of three different areas in Japan presented conflicting results regarding this association. We, thus, investigated the relation between the ACE I/D polymorphism and blood pressure (BP), or the frequency of hypertension, respectively, in 706 Japanese male subjects who participated in the health check-up programme of our hospital. The ACE I/D polymorphism was determined by the polymerase chain reaction technique. Of 706 subjects, 203 were found to have hypertension and the other 503 were found to be normotensive. In all subjects, the frequencies of the DD, ID, and II genotypes were 0.123, 0.432, and 0.445, respectively, and the allelic frequency of the D allele was 0.339. In the younger subjects aged <50 years (n=264), neither systolic nor diastolic BP differed significantly among the genotypes. Conversely, in the older subjects aged > or =50 years (n=442), the systolic BP was significantly higher by 5.9 mmHg in the subjects with the ID genotype than those with the II genotype (P<0.01), and the diastolic BP was significantly higher in the subjects with the DD and ID genotypes by 5.1 and 3.3 mmHg, respectively than those with the II genotype (P<0.05 for each), although age, BMI, percentage of smoking habits, drinking habits, or the use of antihypertensive drugs did not differ significantly among the genotypes. In addition, in the older subjects, the hypertensive subjects showed significantly higher frequencies of the DD and ID genotypes and the D allele than the normotensive subjects. These results demonstrated that there was no significant association of the ACE I/D polymorphism with BP or a prevalence of hypertension in younger Japanese men aged <50 years but there was in older Japanese men aged > or =50 years.     

Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans

Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates angiotensin-(1-7) [Ang-(1-7)]. In humans, the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism determined plasma ACE levels by 40%. In rats, a similar polymorphism determines ACE levels which are inversely associated to NEP activity. The objective of this study is to evaluate the relationship between ACE expression and plasma NEP activity in normotensive subjects and in hypertensive patients. In total, 58 consecutive patients with hypertension, evaluated in our Hypertension Clinic, were compared according to their ACE I/D genotypes with 54 control subjects in terms of both plasma ACE activity and NEP activities. Plasma ACE activity was elevated 51 and 70% in both DD ACE groups (normotensives and hypertensives) compared with their respective ID and II ACE groups (P<0.001). A significant effect of the ACE polymorphism and of the hypertensive status on ACE activity was observed (P<0.001). In normotensive DD ACE subjects, NEP activity was 0.30+/-0.02 U/ml, whereas in the normotensive II ACE and in the normotensive ID ACE subjects NEP activity was increased 65 and 48%, respectively (P<0.001). In the hypertensive DD ACE patients, NEP activity was 0.47+/-0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (P<0.04) and an interaction effect between the I/D ACE genotype and the hypertensive status were also observed (P<0.001). These results are consistent with a normal and inverse relationship between the ACE polymorphism and NEP activity in normotensive humans (as is also observed in rats). This normal relationship is not observed in hypertensive patients.     

Lack of association between ACE gene polymorphism and left ventricular hypertrophy in essential hypertension

The possible association between the insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene and left ventricular hypertrophy (LVH) was investigated in a group of essential hypertensive patients. Seventy-one essential hypertensive patients (35 men and 36 women), aged 51 +/- 1 years, were genotyped by PCR for the I/D polymorphism of the ACE gene. Cardiac morphology and function were assessed by means of M-mode echocardiography. The relative frequencies of the three genotypes, DD, DI, and II, were respectively: 24%, 55%, and 21%. Mean values of left ventricular mass index were 145, 144, and 150 g/m2 for DD, DI, and II genotypes, without significant differences among them (P = 0.82). Likewise, the prevalence of LVH (76%, 64%, and 87%) was not significantly different among the three genotypes (P = 0.23). We conclude that the ACE gene I/D polymorphism is not associated with LVH in essential hypertension. Journal of Human Hypertension (2000) 14, 47-49.     

Angiotensin-converting enzyme gene polymorphism and its association with essential hypertension in a Tibetan population.

There is strong evidence to support the idea that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of essential hypertension (EH) and its complications. However, existing data about the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with blood pressure is conflicting, mainly due to racial differences and environmental exposure status. We therefore conducted a case control study to observe the relationship between ACE I/D polymorphism and EH in a Tibetan population who live in relatively isolated areas and are genetically homogeneous. The study was conducted at stable residential communities in the urban district of Lhasa, the capital of the Tibet autonomous region, China, and 106 unrelated EH patients and 135 normotensIve subjects were recruited. PCR, PCR/RFLP and PCR-SSCP were carried out to study the association between RAS genes and EH. Frequencies for the DD, ID and II genotypes were 27, 47 and 29 in hypertensive subjects, and 15, 60 and 48 in normotensive subjects, respectively. Derived allele frequencies for the I and D alleles were 0.51 and 0.49 in hypertensive subjects and 0.64 and 0.36 in normotensive subjects. There were significant differences in genotype distribution and derived allele frequency between these two groups. The genotype and allele frequencies of the ACE gene differed significantly between hypertensive and normotensive females (p>0.05), but there were no differences in males. In females, the DBP and MAP level were significantly higher for the DD than for the ID and II genotype, and SBP was significantly higher for the DD than for the II genotype. But in males, there were no significant differences in blood pressure among ACE genotypes. The results showed a significant association between the D allele of the ACE gene and hypertension in Tibetan women but not in Tibetan men.     

甘肃省独有少数民族原发性高血压患者与血管紧张素转化酶基因变异的关系

目的:探讨甘肃省2个独有少数民族(东乡族、裕固族)的血管紧张素转化酶(ACE)基因I/D变异是否为原发性高血压(EH)的遗传易感因素。方法:用聚合酶链方法分别检测了东乡族150例、裕固族45例EH患者及2个民族正常人群172例、58例的ACE基因16内含子I/D变异,并分析比较。结果:东乡族EH患者II、ID、DD基因型的分布频率分别是48·0%、34·0%、18·0%,正常血压者分别是47·1%、35·5%、17·4%;裕固族EH患者II、ID、DD基因型的分布频率分别是40·0%、35·6%、24·4%,正常血压者分别是43·1%、39·7%、17·2%。ACE基因的基因型及等位基因分布在EH患者与正常血压者中差异无统计学意义。但ACE基因的DD基因型和D等位基因频率有随年龄增长而逐渐下降的趋势。结论:ACE基因I/D变异可能不是甘肃省2个独有少数民族(东乡族、裕固族)EH的易感因素。     

Association of angiotensin-converting enzyme DD genotype with 24-h blood pressure abnormalities in normoalbuminuric children and adolescents with Type 1 diabetes.

AIMS: To assess the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in children and adolescents with Type 1 diabetes and to evaluate the association between ACE genotype and blood pressure (BP). METHODS: ACE genotypes were assessed in 124 normoalbuminuric, clinically normotensive Type 1 diabetic children and adolescents and 120 non-diabetic controls using polymerase chain reaction. Twenty-four-hour ambulatory BP monitoring was undertaken in all patients. RESULTS: ACE genotypes distributed in patients as follows: 34 (27%) DD, 57 (46%) ID, 33 (27%) II. The distribution was similar in the control group: DD in 28% (33), ID in 45% (54), and II in 27% (33). Patients with DD genotype had higher mean 24-h diastolic BP (73.8 +/- 6.2 vs. 70.2 +/- 5.0 and 69.7 +/- 6.3 mmHg; P = 0.005) and lower diurnal variation in BP (11.8 +/- 4.6 vs. 14.2 +/- 4.2 and 14.8 +/- 4.3%; P = 0.011) compared with ID and II groups. Four patients in the DD group proved to be non-dipper compared with one in the ID and none in the II group (P = 0.026). Twenty-four-hour diastolic blood pressure was independently predictive for AER as dependent variable in the DD genotype patient group (r(2) = 0.12, P = 0.03). CONCLUSIONS: Children and adolescents with Type 1 diabetes do not differ from the non-diabetic population regarding the I/D polymorphism of the ACE gene. ACE gene polymorphism is associated with BP abnormalities in normotensive and normoalbuminuric children and adolescents with Type 1 diabetes.     

I/D gene polymorphism of the angiotensin-converting enzyme and left ventricular hypertrophy. Response to converting enzyme inhibitors

BACKGROUND: The present study was designed to assess whether the angiotensin-converting enzyme (ACE) gene I/D polymorphism influence the ACE inhibitors effect on the regression of left ventricular hypertrophy. METHODS: Sixty hypertensive subjects never treated by antihypertensive drugs, aged 46 +/- 11 years, were included in the study. Follow-up with ACE inhibitor treatment was 60 +/- 26 months. Genotypes for ACE I/D polymorphism (DD, ID or II) were determined by PCR. The left ventricular mass index (LVMI) was assessed by two-dimensional directed M-mode echocardiography. RESULTS: ACE genotype distribution was in agreement with the Hardy-Weinberg equilibrium: 21 patients had the DD genotype, 29 were ID, and 10 were II. At baseline, age, systolic arterial pressure and LVMI didn't differ on the basis of genotype. Body mass index was significantly higher in II than in ID and DD groups. Regression of LVMI with ACE inhibitor treatment was similar in the 3 genotypes (-8.9%, -0.6%, -12.1% in DD, ID and II groups respectively). In addition, decrease of systolic arterial pressure was identical in 3 groups. CONCLUSION: ACE gene I/D polymorphism seems not to influence regression of left ventricular hypertrophy by ACE inhibitors in essential hypertension.     

Angiotensin Converting Enzyme Gene Polymorphism Is Not Related to Essential Hypertension in a Greek Population

Studies in various ethnic groups have shown contradictory evidence on the association of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with essential hypertension. In addition, mistyping of the insertion allele in heterozygotes has been reported. We analyzed the ACE genotype of 98 hypertensive and 84 normotensive subjects of Greek origin. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers were flanking the polymorphic region in intron 16 of the ACE gene. To avoid mistyping of heterozygotes, samples with the DD genotype were also amplified with primers that detect only the insertion allele. The distribution of the DD, ID, and II ACE genotypes was 30, 45, and 23 in hypertensive patients and 29, 40, and 15 in normotensive subjects, respectively. The estimated frequency of the insertion allele was 0.45 in hypertensive and 0.42 in normotensive subjects. The difference was not statistically significant. The results indicate a lack of association between ACE I/D polymorphism and essential hypertension in this Greek population, suggesting that other genes must contribute to the pathogenesis of hypertension. Am J Hypertens 1996; 9:700–702     

Effect of angiotensin-converting enzyme insertion/deletion polymorphism DD genotype on high-frequency heart rate variability in African Americans

Seventy-nine African-American participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) pilot study were genotyped for the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and had spectral power of their high-frequency (HF) heart rate variability (HRV) determined by fast-Fourier transformation. HF HRV was highest in II, intermediate in ID, and lowest in DD (II vs DD, p <0.043) genotypes, thus making an association of the ACE I/D DD genotype with decreased HF HRV that is consistent with the hypothesis that the DD genotype confers susceptibility to increased cardiovascular risk. The urban African-American population we studied had a particularly high cardiovascular risk, and these findings suggest that ACE I/D genotypes may modify that risk.