子痫前期肾素血管紧张素系统基因多态性及其相互作用的相关性研究

目的 探讨血管紧张素转换酶（ACE）基因插入／缺失（I/D），血管紧张素原（AGT）基因M235T，血管紧张素Ⅱ1型受体（AT1R）基因A1166C位点多态性与子痫前期发病的关系。方法 采用聚合酶链反应（PCR）和聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测58例子痫前期孕妇，102例正常妊娠孕妇的ACEI／D，ACTM235T，AT1RA1166C位点多态性。结果 子痫前期组ACEDD型占48．3％（P〈0．05，优势比[OR]2．04），Ⅱ型占8．6％（OR0．34），子痫前期组与对照组相比D等位基因频率显著增加（P〈0．01，OR1．9）。AGTM235T，AT1RA1166C多态性与子痫前期无明显相关。子痫前期三个基因的基因型之间无明显协同作用。结论 ACEDD型可能增加妊娠期高血压疾病患病风险，ACEI／D，AGTM235T，AT1RA1166C多态性在子痫前期发病危险性上无明显协同作用。     

基因芯片技术分析血管紧张素原基因多态性与冠心病的关系

目的探讨中国人冠心病(CHD)患者与血管紧张素原(AGT)基因M235T多态性的关系。方法选择100例CHD患者,同期100例非CHD患者作对照。应用基因芯片技术检测AGT基因M235T多态性,并比较其基因型及等位基因频率,其中CHD组有90人、对照组有79人的AGT基因M235T多态性检测合格。结果 CHD组AGT TT基因型频率与对照组相比有显著性差异,AGT基因多态性与CHD明显相关。T等位基因是CHD的危险因素,可增加CHD发病的2.505倍。性别和年龄对CHD的发病也有影响。结论 AGT基因多态性可能是中国CHD的危险因素。     

血管紧张素原基因M235T多态性与下肢深静脉血栓的关系

目的探讨血管紧张素原（ACT）基因M235T变异与下肢深静脉血栓形成（DVT）的发病关系。方法采用聚合酶链反应及限制性片段长度多态性分析法检测72例DVT患者（DVB组）及80例健康体检者（对照组）AGT基因M235T多态进行检测。结果DVT组ACT基因突变产生的’丌基因型频率明显高于对照组（P〈0．05）。结论AGT基因M235T＇IT基因型与DVT的发病有关。     

血管紧张素原基因M235T多态性与冠心病关系的研究

目的　探讨中国苏皖地区人群血管紧张素原（AgT）基因型的分布及其与冠心病（CHD）的关系。方法　应用突变基因分离聚合酶链（MS-PCR）技术,对106例CHD患者、56例冠状动脉造影正常者以及30名健康献血员AgT基因M235T多态性进行检测。结果　病例组和对照组AgT基因型总体分布无显著差异,而病例组T等位基因频率（0.788）显著高于对照组（0.698）（P＜0.05）。结论　AgT基因M235T多态性中T等位基因是中国苏皖地区人群CHD发病的危险因素之一。     

肥厚型心肌病伴流出道梗阻的心电图表现与彩超图的对照分析

肥厚型心肌病(hypertrophic cardiomyopathy,HCM)临床上较多见,其主要表现为室间隔与左室后壁的异常增厚.伴左室流出道梗阻则是其一种特殊类型,它是以非对称性心肌肥厚和心室腔变小为特征的心肌病变.我们对1999年5月～2002年8月来我院确诊治疗的肥厚型梗阻性心肌病患者32例,进行了心电图及彩超检查和对照分析.现报告如下:     

血管紧张素原基因多态性与冠脉狭窄分析

目的　探讨中原地区人群血管紧张素原 (AGT)基因M2 3 5T多态性分布特点与冠心病及冠状动脉狭窄严重程度的关系。方法　采用聚合酶链反应 -限制性片段长度多态性 (PCR -RFLP)技术检测 12 0例冠心病患者和 80例健康对照者AGT基因多态性。对冠心病组所有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。结果　冠心病组TT基因型频率及T等位基因频率与对照组比较差异无显著性 (P >0 .0 5 ) ,分别为 4 0 .9%、31.2 %和 6 6 %、5 7% ,AGT三种基因型间冠脉病变支数和冠脉危险记分差异也无显著性(P >0 .0 5 )。结论　AGT基因M2 3 5T多态性与冠心病的发生和冠脉狭窄严重程度均无相关性     

超声诊断肥厚型心肌病

肥厚型心肌病根据左室流出道有无阻塞分为梗阻性、非梗阻性和隐匿性心肌病。梗阻性肥厚型心肌病由于二尖瓣或腱索延长及虹吸作用向前移动,导致左室流出道狭窄或梗阻;隐匿性肥厚型心肌病一般情况下无左室流出道受阻,仅在药物或其他因素影响下才出现阻塞现象;非梗阻性肥厚型心肌病除室壁增厚外,无左室流出道梗死。     

血管紧张素原基因多态性在过敏性紫癜患儿中的表达

目的 探讨血管紧张素原(AGT)基因多态性在过敏性紫癜(HSP)患儿中的表达,以推测肾素-血管紧张素系统(RAS)基因型和HSP患儿之间的关联性.方法 30例HSP组为住院确诊HSP的患儿,另取61名正常体检儿童为对照组,经聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)法检测AGT基因型.结果 AGT基因TT型构成比在HSP组与对照组之间分别为29.2%和3.3%(P＜0.01).其中,T等位基因频率在HSP组和对照组分别为59.9%和47.5%(P＜0.05).结论 AGT M235T基因型与HSP患儿有关联,该基因型可作为疾病易感性的标记.     

宁夏回汉族 KCNQ1基因多态性与2型糖尿病的相关性研究

目的：探讨 KCNQ1基因 rs231362位点的多态性对宁夏地区回汉民族2型糖尿病易感性的影响。方法采用 PCR －RFLP 技术对宁夏地区回族、汉族的 KCNQ1基因 rs231362多态性基因型及等位基因频率在正常糖耐量人群和2型糖尿病人群中的分布进行分析。结果（1）两个民族中,KCNQ1基因 rs231362多态性在同民族2型糖尿病组和正常糖耐量组的分布差异无统计学意义;（2）KCNQ1基因 T 等位基因的分布频率在两个民族大致相同,回族 T 等位基因频率为0．05,低于本组汉族人群;（3）两个民族正常糖耐量人中,CC 组与 TC ＋TT 组各指标相比差异无统计学意义（P ＞0．05）,而在糖尿病组,回族与汉族 T 等位基因携带者（CT ＋TT）腰围水平 BMI 和腰臀比显著高于 CC 组（P ＜0．05）,而低密度脂蛋白水平低于 CC 组（P ＜0．05）。结论KCNQ1基因变异与宁夏地区两个民族2型糖尿病不相关。KCNQ1基因 rs231362多态性 CT ＋TT 基因型可能与回汉族2型糖尿病的腹型肥胖有关,且携带 T 等位基因者可能对回族2型糖尿病患者的血脂具有调节作用。     

中国人群非综合征性唇腭裂与MTHFR基因C677T多态性

目的 探讨MTHFR基因C677T多态性与中国人群非综合征性唇腭裂（NSCL／P）发生的关系。方法 应用聚合酶链式反应一限制性片段长度多态性（PCR-RFLP）方法检测MTHFR基因C677T多态性,用病例对照方法进行统计分析。结果 计算TDT,X^2=0.02,P〉0.05;患儿和正常儿童等位基因频数比较,X^2=9．91,P〈0．05;有无家族史比较,差异无显著性。结论 MTHFR基因C677T位点多态与中国人群NSCL／P的发生相关。     

Associations between polymorphisms of endothelial nitric oxide synthase(eNOS) gene G298A,matrix metalloproteinase-3(MMP-3) gene 5A/6A,angiotensinogen(AGT) gene M235T,angiotensin Ⅱ type 1 receptor(AT1R) gene A1166C and risk of restenosis after percutaneo

OBJECTIVE Previous studies had provided controversial results regarding the restenosis risk for eNOS, MMP-3, AGT and AT1 R polymorphisms. The aim of our study was to summarize the relationship between those polymorphisms and risk of restenosis after percutaneous coronary intervention. METHODS Al studies published on the association of e NOS G298 A, MMP-3 5 A/6 A, AGT M235 T and AT1 R A1166 C polymorphism with restenosis were identified by searching the Pub Med, Embase,Cochrane's Library and clinicaltrials.gov. Two authors independently selected studies, assessed the risk of bias(Newcastle-Ottawa Scale) and extracted data. The metaanalysis was performed in Stata 12.0. PROSPERO registration number: CRD 42019135173. RESULTS A total of 18 researches were analyzed in the meta-analysis, including 5 on G298 A, 4 on 5 A/6 A, 6 on M235 T and 7 on A1166 C.Overall, under several models, there were significant associations of elevated restenosis risk for e NOS gene G298 A, MMP3 gene 5 A/5 A, AGT gene M235 T and A1 TR gene A1166 c polymorphism. For G298 A variant eNOS gene, OR_(allele)=1.685(1.269, 2.338), OR_(heterozygote)=2.144(1.490, 3.085), OR_(dominant)=2.078(1.462, 2.954) and OR_(over-dominant)=0.496(0.348, 0.706). For 5 A/6 A variant MMP3 gene, OR_(heterozygote)=0.839(0.722, 0.975), OR_(dominant)=0.846(0.733, 0.976) and OR_(over-dominant)=1.131(1.001, 1.301). For M235 T variant of AGT gene with OR_(heterozygote)=1.594(1.179, 2.155), OR_(dominant)=1.437(1.077, 1.918) and OR_(over-dominant)=0.694(0.555, 0.869). Moreover, positive results were observed in AT1 R gene A1166 C polymorphism under three models with OR_(homozygote)=2.009(1.433, 2.816),OR_(recessive)=1.874(1.353, 2.595) and ORdominant=1.350(1.105, 1.649). There were heterogeneity ranging from low(0.0%) to high(66.2%) levels found during the analysis process, in which ethnicity and intervention type might play a role. CONCLUSION The pooled OR of the present meta-analysis suggested evidence that there was an increase in the risk of restenosis conferred by the G298 A variant of e NOS gene in Caucasian, the 5 A/6 A variant of MMP-3 gene in Asian, the M235 T variant of the AGT gene in Caucasian and the A1166 C variant of A1 TR gene in Asian.     

Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure

AIMS

Racial differences in survival outcomes point towards a genetic role in the pathophysiology of heart failure. Furthermore, contemporary evidence links genetics to heart failure (HF) predisposition. We tested for a difference in prevalence of 10 renin-angiotensin-aldosterone system (RAAS)-related gene polymorphisms between a homogenous population of HF patients and healthy controls.

METHODS

One hundred and eleven healthy volunteers and 58 HF patients were included in this study. The healthy control group consisted of males aged between 18 and 35 years old. The HF group consisted of patients (89.7% male) who were 63.8 ± 7.9 years old, were in New York Heart Association (NYHA) class II-III and had a documented left ventricular ejection fraction (LVEF) ≤ 40% within the previous 6 months. Despite being treated maximally for their condition with angiotensin-converting-enzyme (ACE)-inhibitors and β-adrenoceptor blockers, they continued to be symptomatic and, as such, were a highly specialized and homogeneous patient population. Both groups were composed of Canadian Caucasians. The analyzed polymorphisms were: ACE (I/D), angiotensin-II-receptor-type-1 (AGTR1)(A1166C), angiotensinogen (AGT)(M235T and T174M), endothelial-nitric-oxide-synthase (eNOS)(T-786C and Glu298Asp), adrenergic-receptor-â2 (ADRB2)(Gln27Glu), bradykinin-receptor-β2 (BDKRB2)(+9/−9), aldosterone-synthase (CYP11B2)(T-344C) and adducin-1 (ADD1)(Gly460Trp).

RESULTS

The AGT (T235) allele (P = 0.0025, OR 2.02, 95% CI 1.24, 3.30) was found to be more prevalent in our HF group. The AGT (174M)-AGT (235T) haplotype was also associated with the HF phenotype (P = 0.0069). Exploratory evaluation of gene-gene combinations revealed an indicative association of the AGT (T235)/ACE(D) combined polymorphisms in the HF group (P = 0.02, OR 2.12, 95% CI 1.11, 4.06).

CONCLUSIONS

This study demonstrates that the SNPs of AGT may be associated with HF in our population and that the AGT/ACE gene combination may play an important role in disease predisposition.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The progression and pharmacological response of heart failure-affected patients are subject to interindividual variability.
• t is also acknowledged that the genotype frequency of certain gene polymorphisms varies across different ethnic groups and that a difference in gene polymorphism frequencies between healthy and heart failure patients seems to exist.

WHAT THIS STUDY ADDS

• This study investigated associations between 10 gene polymorphisms of RAAS-related genes with an individual''s susceptibility to heart failure.
• Our data suggest that the angiotensinogen (AGT) 235 single nucleotide polymorphism (SNP) may be associated with heart failure in our population and that the AGT(M174)-AGT(T235) haplotype, as well as the AGT/angiotensin-converting enzyme (ACE) gene combination, may play an important role in disease predisposition.

     

ACE I/D、AGT M235T基因型与伊贝沙坦治疗高血压病降压疗效的关系研究

目的发现高血压患者与血管紧张素Ⅱ受体拮抗剂(伊贝沙坦)降压疗效相关的基因多态性位点。方法符合WHO/ISH高血压诊断标准的轻、中度高血压患者117例,服用伊贝沙坦单药治疗8周,在临床观察疗效的同时,用RFLP及PCR方法对患者血白细胞基因组DNA血管紧素-醛固酮系统基因多态性位点ACE I/D、AGT M235T基因型进行分析。结果含ACE D等位基因的患者服用伊贝沙坦后,收缩压下降幅度明显大于Ⅱ型基因型患者,两者之间有统计学差异(P<0.05);AGT M235T各基因型之间血压下降幅度均无显著差异。结论ACE I/D基因型与伊贝沙坦类药物的敏感性有一定相关性。     

Genetic polymorphisms of the renin-angiotensin system in preterm delivery and premature rupture of membranes.

INTRODUCTION: Premature rupture of membranes (PRM) is a late pregnancy complication commonly associated with preterm delivery (PD). Although several markers related to the renin-angiotensin system (RAS) have been evaluated in certain pregnancy complications, only the angiotensin-converting enzyme (ACE) I/D variant has been studied in PD-PRM. The aim of this survey was to investigate the association of the polymorphisms (angiotensin II type 1 [AT1] receptor T174M and M235T, renin G2805A, ACE I/D and AT1-receptor A1166C) of the genes of RAS in women with PD-PRM. DESIGN: Deoxyribonucleic acid samples from 89 Mexican Mestizo women with PD and PRM and 224-288 controls were studied. Polymorphisms were analysed by polymerase chain reaction-restricted fragment length polymorphism or sequence specific primer assays. RESULTS: For all loci, genotype distribution was in agreement with Hardy-Weinberg expectations in the control group. Significant intergroup difference (case vs. control) was seen for angiotensinogen (AGT) M235T polymorphism, with an increased allele M235 in affected cases (50% vs. 40% in controls). Analysis of two-locus haplotype agrees with an independent segregation of physically unlinked genes. Haplotype AGT 174T-235M was also increased (50% vs. 40% in controls). CONCLUSIONS: Physically unlinked genes involved in RAS segregate independently. The AGT 174-235 region is associated with PD-PRM in this population.     

Angiotensinogen gene variants in a Pakistani hypertensive population of Punjab.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays a key role in blood pressure (BP) regulation. Among the components of the RAAS, the gene for the angiotensinogen (AGT) has been extensively studied. Several studies in different populations link Threonine instead of methionine at position 235 (M235T) and Methinine instead of threonine at position 174 (T174M) polymorphisms with essential hypertension. We were unable to study these polymorphisms in the Punjab population of Pakistan through routine Restriction Fragment Length Polymorphism (RFLP) method. Considering the importance of this region we decided to further investigate the 300 bp region harbouring these two single nucleotide polymorphisms. METHODS: Samples were derived from a larger study group. Polymerase chain reaction amplified fragments were subjected to either RFLP or Single Strand Conformation Polymorphism. Single stranded DNA showing mobility shift on denaturing gel were sequenced. RESULTS: Sequencing confirmed the presence of M235T and T174M polymorphisms in the local population. In addition to these polymorphisms one additional base was found at an identical position in two of the samples. We found a substitution of G with C just adjacent to T174M polymorphism in all seven of our samples studied. CONCLUSIONS: We report two additional bases and one substitution in the angiotensinogen gene of Punjab population. We also suggest that SsmI can be used for the investigation of T174M polymorphism.     

Effects of genetic polymorphisms of the renin-angiotensin system in children with nephrotic syndrome.

BACKGROUND: The renin-angiotensin system (RAS) has been considered to be responsible for the pathogenesis or progression of many diseases which may or may not be related to kidney. Genetic polymorphisms of the various components of the RAS have been associated with differences in the clinical course of several disease states in adults and children. OBJECTIVES: The purpose of our study was to investigate RAS gene polymorphisms in patients with steroid resistant primary focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome responding to steroid therapy. Furthermore, we aimed to investigate whether there was an association between polymorphic alleles and responses to steroid therapy, the degree of renal dysfunction, and prevalence of end-stage renal disease (ESRD). MATERIAL AND METHODS: One hundred and fifty-eight children with the diagnosis of nephrotic syndrome were recruited from the Nephrology unit in the Department of Paediatrics of Ege University. Forty-nine of them were classified as renal biopsy-proven FSGS and 102 patients were considered to have response to steroid treatment. Renal functional impairment was detected in 19 subjects with FSGS and end-stage renal insufficiency in 13 patients. The control group consisted of 287 healthy adult subjects. Angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R) and angiotensinogen (AGT) gene polymorphisms were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. Statistical significance was regarded as p<0.05. RESULTS: There were no statistically significant differences for the C allele of AT1R or the T allele of AGT genes between the children with nephrotic syndrome and control group, but on the other hand statistically significant differences were detected for D allele of ACE gene. There was no significant relationship detected between the D allele of ACE, the C allele of AT1R or the T allele of AGT genes and response to steroid therapy, extent of renal dysfunction and the progression to ESRD. However, there was a significant relationship between T allele of AGT gene and resistance to steroid treatment (OR; 4,837, 95% CI; 1,723-13,577, p=0.01), renal dysfunction (OR; 3,189, 95% CI; 0,999-10,182, p=0.041) and progression to ESRD (OR; 3,852, 95% CI; 1,057-14,040, p=0.03). CONCLUSION: In this study, the angiotensinogen -235T allele was found to be related with steroid resistance, renal dysfunction and progression of ESRD in nephrotic syndrome.     

Association of Angiotensinogen (M235T) Gene Polymorphism with Blood Pressure Lowering Response to Angiotensin Converting Enzyme Inhibitor (Enalapril)

Purpose: It has been suggested that genetic backgrounds, which have an association with essential hypertension, may also determine the responsiveness to ACE inhibitor. We determined the association of angiotensinogen (M235T) gene polymorphism with essential hypertension and the relationship between polymorphism in the angiotensinogen (M235T) gene and blood pressure response to ACE inhibitor (Enalapril) in patients with essential hypertension from northern Indian subjects. Methods: 250 patients with essential hypertension and 250 normal healthy controls from Delhi and surrounding areas were recruited for the investigation. Blood pressure was recorded before and after 6 weeks of treatment with ACE inhibitors, Enalapril. Genotyping were carried out by polymerase chain reaction and Restriction fragment length polymorphism technique. Results: Statistically significant association of T allele was observed with essential hypertension [x2 = 14.67, p = 0.00013, Odds ratio = 1.76 (1.3-2.32) at 95% CI], the relative risk at 95% CI being 1.28 (1.2-1.54). The decrease in systolic blood pressure and diastolic blood pressure after six weeks of treatment of the patients carrying TT genotype (SBP = 26±17.4 mmHg, DBP = 14.83±7.6mmHg) were greater than the groups carrying MT (SBP = 3.0±7.8 mmHg, DBP =6.2±3.0 mmHg) and MM genotypes (SBP = 1.2±0.8 mmHg, DBP = 0.10±12.1 mm Hg. Conclusions: The angiotensinogen (M235T) gene polymorphism is significantly associated with essential hypertension. Patients carrying TT genotype had higher blood pressure lowering response when treated with ACE inhibitor, Enalapril than those carrying MM and MT genotypes suggesting that the T allele may be a possible genetic marker for essential hypertension. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.     

Pharmacogenetic interactions of three candidate gene polymorphisms with ACE-inhibitors or beta-blockers and the risk of atherosclerosis

AIMS: To investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen M235T or angiotensin II receptor type 1 573C/T polymorphism modify the risk of atherosclerosis associated with beta-blocker or ACE-inhibitor therapy. METHODS: Data were used from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects of >or= 55 years. In this study, 2216 subjects with hypertension were included. Three subclinical measurements were used for atherosclerosis, i.e. peripheral arterial disease, carotid atherosclerosis and aortic atherosclerosis. The interaction between antihypertensive drugs and genetic polymorphisms on the risk of atherosclerosis was determined with binary logistic regression analysis. RESULTS: The risk of aortic atherosclerosis associated with long-term (>or=4 years) beta-blocker treatment compared with no use of beta-blockers was higher in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene [synergy index (SI) = 3.36; 95% confidence interval (CI) 1.14, 9.97]. The risk of carotid atherosclerosis associated with long-term ACE-inhibitor treatment compared with no use of ACE-inhibitors was lower in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene (SI = 0.20; 95% CI 0.04, 0.95). CONCLUSION: Overall, the risk of atherosclerosis in hypertensives taking a beta-blocker or ACE-inhibitor-based regimen was not strongly modified by any of the three candidate gene polymorphisms.