The D allele of angiotensin I-converting enzyme gene insertion/deletion polymorphism is associated with the severity of atherosclerosis

BACKGROUND: Angiotensin II is produced primarily by angiotensin I-converting enzyme (ACE) within atherosclerotic lesions and ACE level in plaques correlates with the severity of vessel wall damage. Therefore, we investigated the possible association of ACE gene insertion/deletion (I/D) polymorphism and the severity of atherosclerosis, estimated on the basis of the number of coronary stenoses and critical arterial occlusions observed during coronary angiography. METHODS: The study cohort included 172 patients with angiographically confirmed premature coronary artery disease. The ACE gene I/D polymorphism was genotyped using a PCR method. RESULTS: The frequencies of DD genotype, D allele carrier-state (DD+ID genotypes) and the D allele increased with the number of stenoses in coronary vessels. D allele carriers (DD+ID genotypes) were more frequent in the subgroup of patients with stenoses in at least four coronary vessels than in other patients including subjects with one-, two- and three-vessel disease (97.4% vs. 74.4%, OR=13.05, 95% CI: 1.81-100.00, chi2=9.84, p=0.0017). Furthermore, the D allele was significantly more frequent in patients with critical arterial occlusions (>90%) than in subjects without critical stenoses (61.1% vs. 49.3%, chi2=9.84, p=0.023). CONCLUSIONS: The ACE I/D polymorphism influences individual differences in severity of coronary artery disease and the D allele promotes generation of numerous and critical atherosclerotic lesions.     

Clinical restenosis after coronary stent implantation is associated with the heme oxygenase-1 gene promoter polymorphism and the heme oxygenase-1 +99G/C variant

BACKGROUND: Vascular remodeling after percutaneous coronary stent implantation frequently leads to restenosis. Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous antioxidant bilirubin and carbon monoxide, both of which exert antiinflammatory and antiproliferative effects. The aim of the present study was to evaluate the influence of genetic risk factors combined with the conventional risk factors on the development of coronary restenosis after percutaneous coronary intervention (PCI) with stent implantation. METHODS: The HO-1 gene GT dinucleotide repeat promoter polymorphism and HO-1 +99G/C variant were evaluated in 199 patients with coronary artery disease after coronary stent implantation and control angiography at 6 months after the intervention. Coronary restenosis was confirmed by quantitative angiography. RESULTS: Carriers of the long allele of the HO-1 gene promoter (>29 repeats) had a significantly higher risk of developing restenosis after PCI than noncarriers [odds ratio (OR)=1.9; 95% confidence interval (95% CI), 1.0-3.4; P=0.04]. Interestingly, the allele longer than 29 repeats conferred a significantly higher risk of developing restenosis (OR=3.4; 95% CI, 1.2-9.1; P=0.017) in nonsmokers than in smokers (OR=2.0; 95% CI, 0.7-5.2; P=0.18). CONCLUSIONS: The long allele of the HO-1 gene promoter (>29 repeats) polymorphism, which leads to low HO-1 inducibility, may represent an independent prognostic marker for restenosis after PCI and stent implantation. The effect of the >29 repeat allele is attenuated in smokers, who have chronic exogenous CO exposure.     

汉族人群血管紧张素转换酶基因插入/缺失(I/D)的遗传多态性

背景:血管紧张素转换酶是肾素-血管紧张素-醛固酮系统的重要组成部分,血管紧张素转换酶基因第16内含子内存在一个287bp的Alu序列的插入/缺失(I/D)多态性,与心血管疾病、IgA肾病等疾病的发生具有一定的相关性。目的:分析汉族人群血管紧张素转换酶基因插入/缺失(I/D)多态性的分布,并与已知的其他种族人群进行比较。设计:以健康汉族人为观察对象的观察性实验。单位:江苏省临床免疫学重点实验室,苏州大学附属第一医院检验科,江苏大学医学技术学院检验系。对象:受检者为2005-12/2006-01苏州大学附属第一医院门诊健康体检者241名,男152名,女89名,平均年龄(27±8)岁,均为无血缘关系的苏州地区汉族人,经临床及实验室检查确认排除肝、肾、内分泌、心脑血管疾病。方法:应用聚合酶链反应检测了241名汉族健康体检者血管紧张素转换酶基因I/D多态性等位基因的基因型,并采用荧光标记末端终止法对基因型为D/D、I/I的PCR纯化产物进行DNA测序确认。主要观察指标:血管紧张素转换酶基因I/D基因型,等位基因频率以及与其他种族人群的比较。结果:241名受检者全部进入结果分析。①血管紧张素转换酶的基因型表现为缺失纯合子(DD)、插入纯合子(II)以及缺失和插入杂合子(DI),等位基因D较等位基因Ⅰ缺失一段287bp的核苷酸,即Alu序列。②II,ID,DD基因型频率分别为46.1%,41.5%,12.4%;等位基因I,D频率分别为66.8%,33.2%。③日本人与汉族人群血管紧张素转换酶基因型分布相似,均以II型最常见,DD型最少;欧美人群以ID居多,II型较少。汉族人群与日本人及欧美人群血管紧张素转换酶基因型频率的分布具有种族差异性。与其他各民族人群比较,汉族人群等位基因I显著高于上述各民族(χ2=105.55,P<0.01),等位基因D明显较低(χ2=87.54,P<0.01)。结论:血管紧张素转换酶基因多态性具有种族差异性。了解不同种族人群间血管紧张素转换酶基因多态性的遗传特点,是研究血管紧张素转换酶基因I/D多态性与疾病相关性的基础和前提。     

The relationship between ACE insertion/deletion polymorphism and coronary artery disease with or without myocardial infarction

OBJECTIVES: Presence of the D allele or homozygosity for the deletion (D) allele of the angiotensicen-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been discussed as potent risk factor for coronary artery disease (CAD) and myocardial infarction (MI). The D allele is associated with higher levels of circulating ACE and therefore may predispose one to cardiovascular damage. DESIGN AND METHODS: The study presented here was performed to investigate the association between the ACE genotype and ACE levels. The study group was comprised of 118 angiographically verified CAD patients. 65 patients were MI (+) and 53 patients were MI (-) in this group. A total of 70 healthy individuals were taken as controls. Genomic DNA of 188 subjects was extracted from whole blood. The polymerase chain reaction was used for ACE genotyping, and ACE levels were measured by ELISA. RESULTS: The D allele was found to be significantly more frequent in patients with MI (+) compared with controls (P = 0.024). ACE levels were significantly higher in both MI (-) and MI (+) groups with CAD patients than in controls (P < 0.005). Plasma ACE level was higher in all three groups in the DD genotype compared to II genotype. In groups I and III, this was statistically significant (P < 0.0001, P < 0.01). CONCLUSIONS: It was shown that the I/D polymorphism in the gene for ACE is a genetic risk factor for CAD patients who have a history of MI. ACE insertion/deletion gene polymorphism is also associated with plasma ACE levels in CAD patients with a history of MI.     

ACE基因多态性与PTCA合并支架植入术后再狭窄的相关性研究

目的:探讨血管紧张素Ⅱ转换酶(ACE)基因的多态性与PTCA合并支架植入术后发生支架内再狭窄(ISR)的相关性。方法:选取2001-2003年入我院治疗,成功实施PTCA合并支架植入手术的华东地区冠心病患者共197例,并作为期半年的追踪随访,按照二次冠状动脉造影结果分为术后再狭窄组和未狭窄组,然后运用PCR技术对这197例患者样本进行ACE基因分型,最后采用统计学方法判断ACE基因多态性是否与支架内再狭窄具有相关性。结果:197例患者中再狭窄组为58例,ACE基因型DD、DⅠ、Ⅱ的频率分别为25.9%、39.6%、34.5%;未狭窄组为139例,ACE基因型DD、DⅠ、Ⅱ的频率分别为33.8%、43.9%、22.3%,两组间无显著差异(x2=3.2N).P>0.05)。再狭窄组和未狭窄组的D等位基因的频率分别为52.6%和55.8%,亦无显著差异(x2=3.326.P>0.05)。结论:ACE基因1/D多态性与支架术后再狭窄无相关性。     

Lack of association between angiotensin-converting enzyme gene polymorphism and type I aortic dissection

The relationship between angiotensin-converting enzyme (ACE) gene polymorphism and type I aortic dissection was examined in 205 unrelated hypertensives. A total of 94 patients underwent emergency repair due to type I aortic dissection, confirmed by computed tomography, and the remaining 111 were controls. Polymerase chain reaction was used to confirm that ACE gene polymorphism was due to insertion (I) or deletion (D) of a 287 base pair (bp) DNA sequence within intron 16. The genotype distribution and allele frequency of ACE I/D polymorphism between patients and controls were not statistically significant. When the frequency of at least one D allele carrier (DD or ID genotype) was compared with the II homozygous genotype, there was also no significant difference between the study groups. The findings revealed no association between ACE I/D polymorphism and aortic dissection. We conclude that I/D mutation of the ACE gene does not seem to be a risk factor for aortic dissection.     

Association study of the I/D polymorphism and plasma angiotensin-converting enzyme (ACE) as risk factors for stent restenosis

The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95%). Restenosis rates among genotypes were 31.2% DD, 25.5% ID and 28.8% II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7+/-18.6 units/l compared with 22.8+/-12.8 units/l; P=0.0001) and a strong independent predictor of ISR [OR (odds ratio)=3.70; 95% CI (confidence interval), 2.40-5.71; P<0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR=0.16; 95% CI, 0.04-0.69; P=0.014; and patients with AMI, OR=0.21; 95% CI, 0.061-0.749; P=0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7% DD, 24.3% ID and 17.6% II (P=0.02; DD compared with non-DD OR=1.57; 95% CI, 1.09-2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.     

Increased deformability of red blood cells is associated with a deletion polymorphism of the angiotensin-converting enzyme gene

Angiotensin-converting enzyme (ACE) plays important roles in the renin-angiotensin system. ACE converts angiotensin I to angiotensin II and also inactivates bradykinin, thereby modulating the vascular tone. A polymorphism of the ACE gene, located on chromosome 17, has been found in intron 16, and is characterized by the presence (insertion [I]) or absence (deletion [D]) of a 287-base-pair Alu repeat. Individuals with the D allele of the ACE gene have higher ACE levels and are at higher risk of cardiovascular events. We aimed to investigate the possible relationship between the I/D polymorphism of the ACE gene and hemorheological parameters, including red blood cell (RBC) deformability. The study was performed on 28 healthy young volunteers (13 women and 15 men, mean age 24 +/- 2). The prevalence of the I and D alleles was 30.4% and 69.6%, respectively. The I/I genotype (II) was found in 21.4%, I/D genotype (ID) in 17.9%, and D/D genotype (DD) in 60.7% of the subjects tested. No significant relationship between ACE I/D polymorphism and RBC aggregation or whole blood and plasma viscosity was observed. In contrast, RBC deformability was significantly increased in the subjects with the DD genotype compared with the II (p < 0.05) or the ID (p < 0.01) genotype, and in the subjects with the D allele compared with the I allele (p < 0.01). We suggest that RBC deformability of individuals with the D allele, who have higher risk for cardiovascular pathologies, may have been increased by a compensatory mechanism.     

Angiotensin-converting enzyme insertion/deletion polymorphism is associated with severe hypoxemia in pediatric ARDS

Purpose  

The D allele of the insertion/deletion (I/D) polymorphism of a 287-bp sequence in the angiotensin-converting enzyme (ACE) gene has been associated with an increased activity of this enzyme. Its role in susceptibility to acute respiratory distress syndrome (ARDS) has not been well defined. We hypothesized that ACE I/D genotype in pediatrics is associated with ARDS and plasma levels of angiotensin II.     

基因学干预研究:血红素氧合酶1微卫星多态性表达水平上调的作用

背景人类血红素氧合酶1(Heme Oxygenase-1,HO-1)基因启动子区域有一双核苷酸(GT)n重复序列,有高度多态性,又称为微卫星多态性,体外实验表明通过测定GT重复次数可间接了解人体内HO-1的表达水平.目的探讨HO-1基因启动子双核苷酸GT n重复序列的微卫星多态性与冠状动脉支架术后再狭窄的关系.设计以接受冠状动脉支架置入术的冠心病患者为研究对象的病例对照研究.单位一所大学医院的心内科病房.对象研究对象为1996-04/2002-05北京大学第一医院心内科病房成功接受冠状动脉支架置入术的冠心病患者,共118例.纳入标准支架术后3个月以上行冠状动脉造影随访的冠心病患者;排除标准冠状动脉造影显示原靶病变管腔直径狭窄＜50%和冠状动脉造影随访时间＜3个月的冠心病患者.入选患者年龄(62±10)岁,男92例,女26例,所有患者均签署知情同意书.根据美国心肺血液协会的标准定义,将患者分为支架内再狭窄组与无再狭窄组,分别为68例和50例.方法提取患者外周血DNA,经PCR扩增HO-1微卫星序列后采用Spreadex凝胶电泳来进行基因分型.主要观察指标HO-1基因启动子微卫星基因型频率及其与再狭窄的关系. 结果携带GT重复＜25次等位基因患者的再狭窄率为47.5%,携带两条GT重复均≥25次等位基因患者的再狭窄率为68.4%(P＜0.05).经多元回归分析校正冠心病危险因素及介入治疗的相关影响因素后,两组患者的再狭窄率差异仍有显著性意义(OR=0.418,95%可信区间0.197～0.887,P＜0.05).结论HO-1基因启动子微卫星多态性与再狭窄相关,对冠心病患者冠状动脉支架置入术后的二级预防有十分重要的意义.     

The angiotensinogen gene 235T variant is associated with an increased risk of restenosis after percutaneous transluminal coronary angioplasty

The therapeutic benefit of percutaneous transluminal coronary angioplasty (PTCA) is limited by restenosis in 30-40% of patients. The underlying mechanisms are currently not well understood. Besides clinical and angiographic variables, genetic factors may be involved. In the present study, we investigated the associations between the angiotensinogen T174M and M235T, the angiotensin I-converting enzyme (ACE) I/D and the angiotensin II type 1 receptor A1166C gene polymorphisms and restenosis in 511 patients who had undergone successful PTCA (without stenting) and follow-up angiography. Clinical and angiographic variables were also considered as possible predictors of restenosis. Stenosis severity was estimated by visual inspection of the angiograms. Altogether, 160 patients had restenosis, as defined by a greater than 50% reduction in the diameter of the dilated segment at follow-up angiography compared with the findings immediately following angioplasty. There were significantly more carriers of the angiotensinogen 235T allele and more patients with the ACE DD genotype in the restenosis group than in the no restenosis group, but only the angiotensinogen 235T allele (and not the ACE DD genotype) remained significantly associated with restenosis following multifactorial analyses. No differences between the two groups were found with respect to the other gene polymorphisms. Patients who subsequently developed restenosis had a higher degree of stenosis and more severe lesions before PTCA, as well as less residual stenosis immediately after PTCA. We conclude that the angiotensinogen M235T gene polymorphism may be an independent predictor of restenosis after PTCA.     

血管紧张素转换酶基因多态性与高血压病早期腔隙性脑梗死的关系

INTRODUCTIONDuringthecoursesofcerebrallesionofhypertensivedisease,resin-angiotensinsystemhasplayedanimportantrole,andan-giotensin-convertingenzyme(ACE)isthekeyoneinthesystem.RecentresearcheshaveshowedtherearerelationshipbetweenthepolymorphismofACEgeneandplasmlevelofACEandmanycar-dio-cerebralvasculardiseases.MATERIALSANDMETHODSMaterialsThecasesintheexperimentswouldbedividedintotwogroups:thehypertensiongroupandthecontrolgroup.Inthehypertensiongroup,there79patientswithprimaryhyper…     

吉林地区汉族人ACE基因多态性与2型糖尿病合并冠心病的相关性研究

目的 探讨血管紧张素Ⅰ转换酶(ACE)基因插入/缺失(Ⅰ/D)多态性与吉林地区汉族人2型糖尿病患者合并冠心病的关系.方法 对80例2型糖尿病合并冠心病的患者,60例单纯2型糖尿病患者,60名健康人进行分组对照性研究.抽提人外周血中白细胞的基因组DNA,采用聚合酶链反应(PCR)扩增ACE基因第16内含子的一个287bpAlu的插入/缺失(I/D)基因片段,然后进行1.5%的琼脂糖凝胶电泳,并在紫外线灯下观察荧光带并确认每例的基因型.各组间的基因型频率比较应用Hardy-Weinburg遗传平衡定律检验和χ2检验.等位基因频率比较应用χ2检验.结果 各组间ACE基因的基因型频率分布有显著性差异(P＜0.05),等位基因频率分布无明显差异(P＜0.05).结论 ACE基因的I/D多态性与吉林地区汉族人2型糖尿病合并冠心病的发病无显著相关性.     

CD36 polymorphism and its relationship with body mass index and coronary artery disease in a Korean population.

BACKGROUND: CD36 is a multifunctional membrane receptor and a cell-adhesion molecule that is expressed in platelets, monocytes/macrophages, microvascular endothelial cells, cardiac monocytes and adipocytes. In this study, we investigated whether genetic polymorphisms of the CD36 gene are associated with risk of coronary artery disease (CAD) in a Korean population. METHODS: PCR and polyacrylamide gel electrophoresis or PCR-restriction fragment length polymorphism assays were performed to analyze the following CD36 gene polymorphisms: a (TG) repeat in intron 3 and the base substitution 478C>T (Pro90Ser). A total of 219 patients with significant CAD and 236 control subjects were examined with regard to their genotypes, lipid profiles and other risk factors for CAD. RESULTS: The frequency of (TG) 11- or 12-repeat homozygotes was significantly higher in male CAD patients than in control men (28.4% vs. 15.7%, OR=2.13, p=0.018). Homozygosity for the (TG) 11- or 12-repeat allele was also significantly associated with a higher body mass index (BMI) compared to non-carriers in 134 control men after controlling for age, smoking and hypertension, and explains a 13% BMI variation observed in this study (p=0.015, analysis of covariance). For the 478C >T mutation, which has been reported to be associated with CD36 deficiency, there was no difference in the frequency of the 478T allele between CAD patients and control subjects. However, the 478T allele was found to be closely linked with a (TG) 11- or 12-repeat allele of intron 3 in the control subjects (chi2=18.88, p<0.001). CONCLUSIONS: The (TG) repeat polymorphism in intron 3 of the CD36 gene is associated with a higher BMI and cardiovascular risk for men in a Korean population.     

Meta-analysis of the effect of diabetes on restenosis rates among patients receiving coronary angioplasty stenting

OBJECTIVE: Coronary artery disease is a significant source of morbidity and mortality in patients with diabetes. Angioplasty has been associated with higher rates of restenosis in patients with diabetes. Numerous studies have been performed to determine whether coronary artery stenting would be useful in decreasing rates of restenosis of coronary vessels in patients with diabetes. This meta-analysis was conducted to determine the effect of diabetes on angiographic restenosis in patients undergoing coronary stenting. RESEARCH DESIGN AND METHODS: Six studies were included comprising 6,236 individuals-1,166 with diabetes and 5,070 without. The relationships between restenosis rates and age, the percentage of the study population that was male, and the percentage of the study population receiving insulin therapy were examined. RESULTS: The average restenosis rates among patients with and without diabetes were 36.7 and 25.9%, respectively. Restenosis rates were higher among older populations and populations in which a greater percentage of patients with diabetes were treated with insulin, but they did not vary according to the percentage of men in the studies. The odds ratio of coronary artery restenosis associated with diabetes was 1.61 (95% CI 1.21-2.14, P = 0.004) in univariate logistic regression models, but decreased to 1.30 (0.99-1.70, P = 0.055) after controlling for age in multivariate models, suggesting that the higher restenosis rates found in patients with diabetes can in good part be explained by the older ages of patients with diabetes in these studies. CONCLUSIONS: Although diabetes is a risk factor for restenosis after coronary angioplasty stenting, the apparent effect of diabetes on restenosis rates in the published literature is overstated and was reduced in this meta-analysis by approximately half after adjusting for differences in age.     

晚发性抑郁症与血管紧张素转化酶基因多态性关系研究

目的探讨晚发性抑郁症(LOD)与血管紧张素转换酶(ACE)基因第16内含子中Alu重复序列的插入/缺失(In-sertion/Deletion,I/D)多态性的关系。方法入组183例60~85岁老年人,晚发性抑郁症组(93例,下称LOD组)和正常对照组(90例,下称对照组),用聚合酶链式反应(PCR)法进行ACE基因I/D多态性分型。结果LOD组和对照组间基因型频率及等位基因频率分布差异无显著(χ2=0.241,P=0.886;χ2=0.127,P=0.722),各基因型亚型患者在年龄、性别、发病次数、病程、HAMD评分、有无精神病性症状、有无自杀企图间差异无显著(P均>0.05)。结论ACE基因I/D多态性与晚发性抑郁症无显著相关性。     

Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease

The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene for the mediation of initial endothelial cell damage seen in arteriosclerosis. Although the association of ecNOS polymorphisms with hypertension has been studied extensively, there is little information regarding its association with coronary artery disease (CAD). We decided to study a 27 base-pair tandem repeat polymorphism in intron 4 of the ecNOS gene in 1043 individuals (413 controls, 630 patients with CAD) who consecutively underwent coronary angiography at our institution. The frequencies of the genotypes drawn from 1038 individuals were 0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with CAD for the ecNOS4b/b, ecNOS4b/a and ecNOS4a/a genotypes, respectively (p=n.s). There was no shift of the genotype frequencies from the expected distribution based on the Hardy-Weinberg equilibrium. Neither the rare ecNOS4a allele nor the ecNOS4a/a genotype conferred an independent risk factor for CAD in subgroups, e.g. smokers, diabetic individuals, hypertensive individuals and individuals with a low conventional risk for CAD. In five individuals we identified an additional 27-bp repeat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the ecNOS4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as the ecNOS4a/a genotype did not show a general association with CAD in the studied European population. Even in high-risk subgroups the ecNOS4a/4a genotype did not represent an independent risk factor for CAD. In addition, the severity of CAD was not associated with the ecNOS4a allele/ecNOS4a/a genotype. Key words : Coronary artery disease; endothelium; nitric oxide; polymorphism; synthase     

血管紧张素转化酶基因I/D多态性与维吾尔族高血压合并阻塞性睡眠呼吸暂停低通气综合征患者左心室肥厚的关系

目的探讨血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与维吾尔族高血压合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者左心室肥厚(LVH)的关系。 方法选取2015年1月至2016年12月于新疆医科大学第一附属医院高血压科首诊住院,且未服用血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂(ACEI/ARB)类降压药物的维吾尔族高血压合并OSAHS患者,共72例,行多导睡眠呼吸监测、动态血压、心脏彩超等检查,聚合酶链式反应(PCR)和琼脂糖凝胶电泳技术测定ACE基因多态性。根据左心室质量指数分为左心室肥厚组(LVH组,n＝24)和非左心室肥厚组(NLVH组,n＝48),比较两组间基因型及基因频率的差异,使用多因素Logistic回归分析左心室肥厚的影响因素。 结果高血压合并OSAHS患者LVH组ACE基因型频率分别为：II(37.50%),ID(20.83%),DD(41.67%),等位基因频率分别为：I(48.00%),D(52.00%),与NLVH组[II(47.92%),ID(37.50%),DD(14.58%),I(67.00%),D(33.00%)]比较,差异有统计学意义(χ²＝6.75,4.70;均P<0.05);对左心室肥厚影响因素进行多因素Logistic回归分析,呼吸暂停低通气指数(AHI)(OR＝6.20,95%CI：1.44～26.77;P<0.05)、DD基因型(OR＝4.61,95%CI：1.05～20.31;P<0.05)是维吾尔族高血压合并OSAHS患者发生LVH的独立危险因素。 结论ACE基因I/D多态性与维吾尔族高血压合并OSAHS患者发生LVH有关,其中DD基因型维吾尔族患者更易发生LVH。     

Detection of a novel exon 4 low-density lipoprotein receptor gene deletion in a swiss family with severe familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant disease which results in 2-3-fold elevated cholesterol levels and in accelerated atherosclerosis. FH is caused by small mutations or larger rearrangements in the low-density lipoprotein receptor (LDLR). Here, we report that screening the LDLR gene in a Swiss family (n = 15) with clinical symptoms of FH by combined single strand conformation polymorphism and long-distance PCR identified a novel 1.3 kb deletion in the LDLR. The deletion eliminated exon 4 of the LDLR presumably by recombination between two identical 25 bp repeats present in intron 3 and 4. The 25 bp sequence in intron 3 is part of an Alu repeat, whereas no homology to Alu repeats was found for the intron 4 region. This 1.3 kb LDLR deletion allele cosegregated with elevated cholesterol levels over three generations. Even on high-dose statin therapy, carriers of the deletion averaged 1.6 times higher cholesterol levels and 1.9 times higher apolipoprotein B-100 (apoB-100) levels than non-carriers who had lipid and apoB-100 levels within the range of the Swiss population. Most affected members of the first and second generation of this family had experienced a first myocardial infarction (MI) before the age of 55 years and most LDLR gene deletion carriers older than 40 years showed severe coronary artery disease (CAD). Hence, we conclude that deletion of exon 4 in the LDLR gene drastically decreases low-density lipoprotein binding leading to severe hypercholesterolemia.     

Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease

The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene for the mediation of initial endothelial cell damage seen in arteriosclerosis. Although the association of ecNOS polymorphisms with hypertension has been studied extensively, there is little information regarding its association with coronary artery disease (CAD). We decided to study a 27 base-pair tandem repeat polymorphism in intron 4 of the ecNOS gene in 1043 individuals (413 controls, 630 patients with CAD) who consecutively underwent coronary angiography at our institution. The frequencies of the genotypes drawn from 1038 individuals were 0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with CAD for the ecNOS4b/b, ecNOS4b/a and ecNOS4a/a genotypes, respectively (p = n.s). There was no shift of the genotype frequencies from the expected distribution based on the Hardy-Weinberg equilibrium. Neither the rare ecNOS4a allele nor the ecNOS4a/a genotype conferred an independent risk factor for CAD in subgroups, e.g. smokers, diabetic individuals, hypertensive individuals and individuals with a low conventional risk for CAD. In five individuals we identified an additional 27-bp repeat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the ecNOS4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as the ecNOS4a/a genotype did not show a general association with CAD in the studied European population. Even in high-risk subgroups the ecNOS4a/4a genotype did not represent an independent risk factor for CAD. In addition, the severity of CAD was not associated with the ecNOS4a allele/ecNOS4a/a genotype.