飞行员中血管紧张素转换酶基因插入或缺失多态性研究

为了解飞行员血管紧张素转换酶(ACE)基因插入或缺失（I/D）多态性情况,探讨ACE基因多态性与飞行员耐力可能的关系,用聚合酶链反应（PCR）扩增技术检测118例飞行员和96例健康对照者的ACE基因I/D多态性。 结果位于ACE基因内含子16的I/D多态性经PCR扩增后呈三种基因型：纯合子插入型（II）、纯合子缺失型（DD）和杂合子插入或缺失型（I/D）。飞行员组II基因型（44.07%）和I等位基因频率（0.65）显著高于健康对照组(分别为31.25%和0.52)。 结果表明ACE I基因有可能在飞行员的飞行耐力中起重要作用。 Abstract:In order to understand insertion/delation (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in pilots,and to explore the relationship between ACE gene I/D polymorphism and the perfomance of the pilots,the polymerase chain reaction (PCR) was used to determine the genotypes for an I/D polymorphism in intron 16 of the ACE gene in 118 pilots and 96 healthy subjects as controls.The result showed that the I/D polymorphism in intron 16 of the ACE gene was categorized into three genotypes: two deletion alleles (genotype DD),heterozygous alleles (genotype ID),and two insertion alleles (genotype II).The genotype II and I allele frequency were significantly higher in pilots (44.07% and 0.65) than that in healthy subjects (31.25% and 0.52).It is suggested that I gene of ACE may play a role in perfomance of the pilots.     

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。     

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.     

中国优秀女子足球运动员ACE基因I/D多态性与运动能力的关联研究

人类运动能力与血管紧张素转换酶(ACE)基因的多态性密切相关。采用PCR-RFLP方法测定15名中国国家队女足运动员与25名普通大学生的ACE基因的I/D多态性。研究结果表明,女子足球运动员等位基因频率为I=51.7%,D=48.3%,基因型频率为II=36.7%,I/D=30%,DD=33.3%;对照组等位基因频率为I=35%,D=65%,基因型频率为II=20%,I/D=30%,DD=50%。经卡方检验符合Hardy-Weinberg遗传平衡定律,两组间基因型频率和等位基因频率没有显著差异,中国足球项目的高水平运动员女子更倾向于I等位基因的高表达。     

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。     

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。     

汉族男性血管紧张素转化酶基因I／D多态性与耐力训练敏感性的关联研究

目的:探讨耐力训练对有氧能力的影响与血管紧张素转化酶(ACE)基因I/D(插入/缺失)多态性的关联性,以探寻影响耐力训练敏感性的基因标记.方法:选择102名北方汉族新兵,进行18周的5 km跑训练,测定训练前后最大摄氧量(VO2max)、通气无氧阈(VT)和定量负荷时动态左心室结构与功能指标,并应用PCR-AFLP方法检测其ACE基因I/D多态.结果:耐力训练后、VO2max、VT和左心室结构与功能均发生了良好的顺应性改变; ID型和Ⅱ型的△VO2max显著高于DD型(P<0.05),△VO2max的组间差异有显著性(P<0.05),Ⅱ型的△VO2VT显著高于DD型(P<0.05).结论:Ⅰ等位基因在VO2max和VT的训练敏感性方面具有明显的遗传优势,Ⅱ基因型与VT训练敏感性有一定关联,未发现I/D多态性与左心室动态功能指标的训练敏感度之间有关联关系.     

ACEⅠ/D基因多态性与儿童原发性肾病综合征的相关性分析

为探讨血管紧张素Ⅰ转化酶(ACE)基因插入/缺失(Ⅰ/D)多态性与儿童原发性肾病综合征(PNS)的相关性。我们选取PNS组患儿103例,其中激素敏感组54例,激素耐药组49例,正常组为健康儿童114例,采用聚合酶链反应技术(PCR)分析ACE基因Ⅰ/D多态性与在各组中的分布,并进行统计学分析。结果显示PNS组与正常组ACEⅠ/D基因型及等位基因频率分布比较差异无统计学意义,激素敏感组与激素耐药组ACEⅠ/D基因型及等位基因频率分布比较差异也无统计学意义。本研究表明ACEⅠ/D基因多态性与PNS的发生无明确关联;ACEⅠ/D基因多态性与激素治疗效应也无明确关联。     

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.     

云南傣族、汉族HLA-G基因14bp插入/缺失多态性研究

14bp插入/缺失多态性是指存在于HLA-G基因第8外显子3′非翻译区(3′UTR)的一个插入/缺失多态,因其能影响HLA-GmRNA的稳定性,并进一步影响HLA-G蛋白的翻译而受到广泛关注。文章采用PCR和电泳技术对云南傣族和汉族两个人群进行了HLA-G基因14bp插入/缺失多态性的检测分析,结果显示傣族和汉族人群+14bp等位基因频率分别为31.97%和40.87%,+14bp/+14bp基因型频率分别为8.20%和17.31%,+14bp/-14bp基因型频率分别为47.54%和47.11%。与国内外已报道的其他人群的数据比较表明:云南汉族群体中HLA-G基因14bp插入/缺失的分布与其他群体相似;傣族则有自己独特的基因型和等位基因分布特点,推测其可能受到了遗传漂变的作用,但不排除自然选择作用的影响。     

Prevalence of the Angiotensin I Converting Enzyme Gene Insertion/Deletion Polymorphism in a Healthy Turkish Population

Angiotensin converting enzyme (ACE) plays an essential role in the renin–angiotensin system. It converts angiotensin I to angiotensin II and inactivates bradykinin and tachykinins. Numerous studies have been published investigating associations of the ACE gene I/D polymorphism with various pathophysiological conditions. We examined the prevalence of the ACE I/D polymorphism in a sample of healthy volunteers from western Turkey, including 1063 healthy Turkish controls. Analysis of the ACE I/D gene polymorphisms by polymerase chain reaction found frequencies of 16.1% for the II genotype, 47.7% for the ID genotype, and 36.2% for the DD genotype. The allele frequency was 39.9% for the I alleles and 60.1% for the D allele. This study demonstrates that the allele and genotype frequency values for the Turkish population are similar to previously published frequencies for Caucasian populations.     

Insertion/deletion polymorphism of the angiotensin converting enzyme gene in coronary artery disease in southern Turkey

Genetic factors are important in the pathogenesis of coronary artery disease (CAD). Angiotensin converting enzyme (ACE) gene insertion(I)/deletion(D) polymorphism is one of the genetic factor found to be related with CAD. We investigated the association between I/D polymorphism of the ACE gene and the presence of CAD. Three hundred and seven patients (187 males and 120 females, aged between 35-80, mean 54.3 +/-9.8 years) who underwent diagnostic coronary angiography were included in the study. ACE I/D polymorphism was detected by polymerase chain reaction. Of the 307, 176 had CAD. The most frequently observed genotype in all subjects was ID (47.9 %). However, in patients with CAD the frequency of II genotype was lower whereas DD genotype was higher compared to the controls (p < 0.05). The number of D allele carrying subjects were also higher (p < 0.05) in CAD patients. The logistic regression analysis indicated that the ACE D allele is an independent risk factor (odds ratio = 1.48, 95 % CI = 1.01-2.18, p < 0.05). In conclusion, the I/D polymorphism of ACE gene (carrying D allele) is an independent risk factor for CAD in the studied Turkish population.     

Association of AGTR1 (A1166C) and ACE (I/D) Polymorphisms with Breast Cancer Risk in North Indian Population

Renin angiotensin system (RAS) comprising Angiotensin converting enzyme (ACE), Angiotensin II (Ang II) and its receptor Angiotensin II receptor type I (AGTR1), plays a critical role in several diseases including cancer. A single nucleotide polymorphism (SNP) A1166C located in 3′ untranslated region (UTR) of AGTR1 and an insertion/deletion (I/D) polymorphism present in intron 16 of ACE gene have been associated with many diseases, but their association with Breast cancer (BCa) is still debatable. Here, we for the first time investigated the association of these polymorphisms in a North Indian BCa cohort including 161 patients and 152 healthy women. The polymorphisms were evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) respectively. The association between these polymorphisms and BCa risk was estimated by calculating Odds Ratio (OR) and chi-square (χ²) test. The DD genotype/D allele of ACE (I/D) polymorphism and “AC and CC” genotype/C allele of AGTR1 (A1166C) polymorphism were associated with higher risk of BCa when evaluated independently. Furthermore, interaction analysis of “AC and CC” and DD genotype and combination of “C and D” alleles of both polymorphisms revealed significantly greater BCa risk than that observed independently. Conclusively, women harboring “AC or CC” genotype/C allele for AGTR1 (A1166C) polymorphism and DD genotype/D allele for ACE (I/D) polymorphisms have a predisposition to develop more aggressive disease with advanced staging and larger tumor size. Our study indicates importance of genetic screening based on these polymorphisms for women, who may have higher risk of BCa.     

Modification of the coronary artery disease risk associated with the presence of traditional risk factors by insertion/deletion polymorphism of the ACE gene

Cigarette smoking, hypercholesterolemia, and obesity influence the renin-angiotensin system (RAS) functions including an increased synthesis of the angiotensin I converting enzyme (ACE). Thus in the present work we explore the interactions of the ACE gene insertion/deletion (I/D) polymorphism and traditional risk factors. The study cohort included 341 subjects composed of 172 patients with angiographically confirmed CAD and 169 blood donors without a history of cardiovascular diseases. The I/D polymorphism was genotyped using polymerase chain reaction (PCR) methodology. To determine the interactions between the ACE genotypes and traditional risk factors the epidemiologic approach was used (4 x 2 tables and the synergy measures). The frequency of the DD genotype was significantly higher in patients than in controls (33.7% versus 21.3%, odds ratio [OR] = 1.88, 95% CI; 1.13-3.15, p = 0.010), but greater differences were found in males (35.7% versus 20.5%, OR = 2.15, 95% CI: 1.14-4.04, p = 0.010). We found a synergy of the DD genotype with smoking (SI = 1.88, SIM = 1.22), total cholesterol > or =5 mmol/l (SI = 2.12, SIM = 1.31) and elevated low density lipoprotein (LDL) cholesterol level (> or =3 mmol/l) (SI = 1.78, SIM = 1.14). The presence of the D allele (DD + ID subjects) also increased the risk of coronary artery disease (CAD) associated with the presence of elevated total cholesterol and LDL cholesterol (SI = 1.69, SIM = 1.18, in both cases), elevated level (> or =1.7 mmol/l) of triacylglycerols (SI = 1.81, SIM = 1.18) and overweight/obesity (SI = 4.25, SIM = 2.36). In each case the estimated CAD risk was greater than that predicted by assuming the additivity of effects (the risk increased from 69% for the D allele - total cholesterol interaction to 325% for the D allele - overweight/obesity). The statistical significance was also confirmed by a multiplicative model of synergy. The DD genotype/D allele of the ACE gene increases the risk of CAD associated with the presence of traditional risk factors.     

Insertion/deletion polymorphism of angiotensin-converting enzyme gene--risk factor for coronary artery disease in the Tuzla region population (Bosnia and Herzegovina)

Angiotensin II is the major effector molecule of renin-angiotensin system; its production can be conveniently interrupted by angiotensin-converting enzyme (ACE). Typical plasma levels of ACE accompany the I/D polymorphism; however, a controversy exists as to whether the DD genotype of the ACE polymorphism affects the risk for the development of coronary artery disease (CAD) and to what extent the ACE polymorphism is associated with CAD in different populations. We compared the I/D polymorphism in 212 CAD patients younger than 50 years with 165 healthy control individuals. They were all from the Tuzla region in Bosnia and Herzegovina. Patients with CAD had a higher prevalence of the DD genotype (36.3%) than controls (25.6%). The odds ratio for the ACE DD genotype in CAD patients was 1.7 (95% confidence interval 1.0-2.7; p < 0.05). We may conclude that the D/D genotype of the ACE gene polymorphism is associated with an increased risk for CAD in the Bosnian population.     

Deletion polymorphism of the angiotensin I-converting enzyme gene in elderly patients with coronary heart disease

Controversy exists as to whether the deletion/deletion (DD) genotype of angiotensin l-converting enzyme (ACE) gene polymorphism is associated with coronary heart disease (CHD). There are only a few studies dealing with this issue in the elderly, also with controversial results. The aim of this study was the assessment of correlation between genetic markers and the risk of CHD in the elderly. The results indicated DD genotype importance for CHD in the elderly as proven by discriminant analysis (chi2 = 25.77; df = 16; p = 0.0620). However, the use of univariate method demonstrated no correlation between DD genotype of ACE gene polymorphism and coronary artery disease. D allele of ACE gene was associated with higher activities of ACE plasma. A weak, but increased risk of MI is associated with high frequency of DD genotype in the elderly. Strong correlation between ACE polymorphism and ACE plasma activities was demonstrated.     

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM

The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been shown to be associated with cardiovascular and renal diseases in diabetes mellitus, but the mechanism underlying this association is not known. In addition, recent studies of the effect of the ACE gene on blood pressure have yielded conflicting results. Therefore, we studied the association of the ACE gene I/D polymorphism with glucose intolerance and insulin resistance, and the contribution of this locus to genetic susceptibility to hypertension in non-insulin-dependent diabetic mellitus (NIDDM). We analysed the ACE genotype in 84unrelated NIDDM patients with a known disease duration of less than 1year and in 115age- and sex-matched controls. The I/D polymorphism was determined by the polymerase chain reaction. There were no differences in ACE genotype distribution and allele frequencies between patients with NIDDM and nondiabetic controls. The frequencies of the D and Ialleles in both groups were identical, viz., 0.65 and 0.35, respectively. The NIDDM patients with the DD genotype had significantly higher blood glucose levels in the oral glucose tolerance test than those with the other genotypes; the incremental glucose area under the curve in the order of II, ID, and DD was 7.2 ± 2.4, 9.2 ± 4.0, and 10.7 ± 2.7mmol/l · h (II vs ID vs DD, P=0.0066 by ANOVA). No significant difference was found between the ACE genotype and serum insulin values. Similarly, there were no differences in body mass index, blood pressure, or serum lipids between the three genotypes. Among the nondiabetic controls, there was no statistically significant association of the I/D polymorphism with serum lipids, blood glucose levels, serum insulin concentrations, or blood pressure values. In conclusion, NIDDM patients with the DD genotype have higher blood glucose levels and are more glucose intolerant; this may help to explain the reported association between the Dallele and vascular complications in NIDDM. Received: 15 September 1997 / Accepted: 13 November 1997     

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).     

Angiotensin-converting enzyme gene polymorphisms and T2DM in a case�Ccontrol association study of the Bahraini population

Bahrain has one of the highest incidence rates of type 2 diabetes mellitus (T2DM). Development of diabetic nephropathy (DN) as a complication was noticed in some patients while absent in others. This interesting observation raises the role of certain genetic risk factors for the development of DN. Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism was found to be associated with T2DM. While some patients have predisposition to DN in the population, others have negative association. The present case-control association study was designed to investigate the association of ACE I/D polymorphism in T2DM patients in Bahrain especially in those who developed DN. A total of 360 T2DM patients (110 with DN and 250 without DN) and 360 healthy (non-diabetic) age-matched subjects were recruited for this study for comparison. The presence (insertion)/absence (deletion) (I/D) polymorphism of a 287-bp Alu1 element inside intron 16 of the ACE gene was investigated using PCR-gel electrophoresis. The results show that the distribution of the homozygote DD genotype of the ACE gene was high among Bahraini T2DM patients compared to the healthy non-diabetic subjects. In addition, the distribution of the deletion (D) allele was high among Bahraini T2DM patients with DN when compared to the healthy non-diabetic subjects. However, there was no significant difference in the distribution of ACE I/D allele and genotypes between DN patients when compared to those T2DM patients without DN. The results obtained in this study are in closely agreement with some previous reports which show a strong association of ACE polymorphism with T2DM patients, yet not a risk factor for development of DN.