1.Association of angiotensinogen gene M235T variant with hypertrophic cardiomyopathy.
Si-yu CAI ; Yu-ping SHI ; Feng YU ; Geng XU
Chinese Journal of Medical Genetics 2004;21(3):280-282
OBJECTIVETo evaluate the influence of the angiotensinogen(AGT) gene M235T variant on the prevalence and severity of hypertrophic cardiomyopathy(HCM).
METHODSThe authors conducted a case-control study on 152 subjects, including 72 HCM patients and 80 normal controls. Polymerase chain reaction(PCR) combined with restriction fragment length polymorphism(RFLP) was used to detect the M235T variant of AGT gene. Interventricular septum thickness, left ventricular posterior wall thickness and apical wall thickness were measured by means of M-mode echocardiography under two-dimensional guidance in the parasternal long-axis plane and apical two- and four-chamber views.
RESULTS(1) The genotype distributions of AGT gene in both groups were in agreement with Hardy-Weinberg equilibrium. (2) The genotype distributions of the M235T variant differed significantly in HCM patients and controls(chi-square=6.090 P<0.05). The frequencies of TT genotype and T235 allele in HCM patients were higher than did the patients in controls(TT genotype 0.63 vs 0.45 OR=2.037 95%CI 1.064-7.899 P<0.05 T235 allele 0.78 vs 0.64 OR=1.990 95%CI 1.197-3.308 P<0.01). (3)The patients with the TT genotype had significantly greater mean left ventricular maximal wall thickness than did the patients with the MM and MT genotypes [(19.1+/-4.8) mm vs(15.3+/-2.6)mm and(16.2+/-5.1)mm F=4.261 P<0.05].
CONCLUSIONThe variant M235T of the AGT gene is significantly associated with HCM in this population. The genotype TT or allele T might be a genetic risk factor for the development and extent of hypertrophy in HCM patients.
Adult ; Aged ; Angiotensinogen ; genetics ; Cardiomyopathy, Hypertrophic ; genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic
2.Relationship between six single nucleotide polymorphisms of angiotensinogen gene and essential hypertension.
Yan LIU ; Wei JIN ; Zheng-wen JIANG ; Kui-xing ZHANG ; Hai-hui SHENG ; Lin JIN ; Ya-yun SHENG ; Wei HUANG ; Jin-de YU
Chinese Journal of Medical Genetics 2004;21(2):116-119
OBJECTIVETo evaluate the relationship of six single nucleotide polymorphisms(SNPs) and their haplotypes of angiotensinogen(AGT) gene to essential hypertension(EH) in Chinese Han population.
METHODSThe genotypes in 185 patients with EH and 185 healthy controls were determined by the method of ABI PRISM SNaPshot Multiplex Kit using six AGT gene polymorphisms at position -217(G/A), -152(G/A), -20(A/C) and -6(G/A) in the promoter region and T174M, M235T in exon 2.
RESULTSThe distribution of AGT genotypes and alleles frequencies showed no significant difference between the group of EH and group of controls (P>0.05). However, haplotype analysis revealed that H4 haplotype frequency, which included -152A, -20C, -6A and 235T alleles, was significantly increased in the group of EH (P<0.05).
CONCLUSIONG-152A, A-20C, G-6A and M235T polymorphisms of AGT gene might play an important role in the occurrence of EH in Chinese Han population.
Adult ; Aged ; Angiotensinogen ; blood ; genetics ; Female ; Haplotypes ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide
3.Association of Angiotensin-Converting Enzyme and Angiotensinogen Gene Polymorphisms with Preeclampsia.
Hyunah CHOI ; Ja Young KANG ; Hong Sun YOON ; Seung Suk HAN ; Chang Sun WHANG ; In Gul MOON ; Hyun Ho SHIN ; Jeong Bae PARK
Journal of Korean Medical Science 2004;19(2):253-257
We tested the hypothesis that angiotensin-converting enzyme (ACE) and angiotensinogen gene polymorphism influence the incidence, development and outcome of preeclampsia. Subjects were recruited from 90 Korean patients with preeclampsia during pregnancy and 98 age-matched controls. After isolation of DNA, polymerase chain reactions (PCR) were carried out to detect polymorphism of the ACE and angiotensinogen. M235T and T174M genotypes of angiotensinogen were determined by digestion with restriction enzyme endonuclease Tth 111-I and NCo I, respectively. The frequency of DD genotype was significantly greater in preeclampsia (0.36) than in controls (0.14) (p<0.05). The frequency of D allele was 0.55 in preeclampsia and 0.40 in controls (p<0.05). There were no differences in the onset of preeclampsia and pregnancy outcomes according to the ACE genotypes. There was no difference in the frequency of a allele of angiotensinogen M235T between the groups (0.79:0.78 in preeclampsia : controls). The frequency of T allele of angiotensinogen T174M gene was slightly increased, but not significantly, in preeclampsia (0.11) than in controls (0.07). In a multivariate analysis, only ACE genotype was associated with the development of preeclampsia (beta=0.27, p=0.05). In conclusion, a molecular variant of ACE, but not angiotensinogen, gene is associated with preeclampsia in Korean women.
Adult
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Angiotensinogen/*genetics
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Female
;
Gene Frequency
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Genotype
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Human
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Korea
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Peptidyl-Dipeptidase A/*genetics
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*Polymorphism (Genetics)
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Pre-Eclampsia/*genetics
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Pregnancy
4.Gene polymorphisms of rennin-angiotensin system and coronary artery thrombosis disease.
Tie-Nan ZHU ; Jia-Qi PAN ; Zhu-Jun SHEN ; Yong-Qiang ZHAO ; Ti SHEN
Journal of Experimental Hematology 2004;12(5):674-679
To investigate the distribution frequencies of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II I type receptor (AT1R) genotypes in Chinese, to find the relationships between polymorphisms of ACE, AGT and AT1R gene, and coronary artery thrombosis disease (CATD) and to study the interactions of themselves, PCR and PCR-RFLP techniques were performed to determine the genotypes of ACE, AGT and AT1R gene in CATD group (192 cases) and control group (110 cases). The results showed that (1) genotype frequencies of the three polymorphisms in the control group were 12.2% (DD), 43.9% (ID), and 43.9% (II) for the ACE I/D polymorphism; 8.2% (MM), 36.7% (MT), and 55.1% (TT) for AGT M235T polymorphism; 91.8% (AA), 8.2% (AC) for AT1R A1166C polymorphism respectively; (2) there were no significant differences between patients in either the control group, the non-MI group, or the MI group in any genotype frequency of all these three genes (P >0.05). (3) the odds ratio for CATD in subjects carrying both AT1R-AC and AGT-TT genotype was 3.517 (95% CI 0.988 - 12.527), compared with those carrying AT1R-AA and AGT-TT genotype and was 15.000 (95% CI 1.940-115.963), compared with those carrying AT1R-AC and AGT-MM/MT genotype. In subjects with AT1R-AC genotype, there was also a great difference of ACE D allele frequency between control group and CATD group (P=0.017). It is concluded that genotype frequencies of ACE I/D polymorphism, AGT M235T polymorphism, and AT1R A1166C polymorphism were obviously different from those in western countries. Although these three polymorphisms were not independent risk factors for CATD or myocardial infarction (MI) in Chinese, AT1R-AC genotype has a significant synergistic effect with AGT-TT genotype. There is also a obvious interaction between AT1R-AC genotype and ACE D allele.
Angiotensinogen
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genetics
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Coronary Thrombosis
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genetics
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Genotype
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Humans
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Peptidyl-Dipeptidase A
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genetics
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Polymorphism, Genetic
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Receptor, Angiotensin, Type 1
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genetics
5.The relationship between haplotypes of angiotensinogen gene and essential hypertension.
Xiangdong KONG ; Sizhong ZHANG ; Yuxia YANG ; Keqin ZHENG ; Yu TONG ; Jiajun SHI ; Kelan ZHANG ; Zhiguang SU ; Wei CHENG
Chinese Journal of Medical Genetics 2002;19(6):488-490
OBJECTIVETo investigate the relationship between the polymorphism of angiotensinogen gene (AGT) and the risk for hypertension in a Chinese population.
METHODSThree polymorphisms of AGT gene were analyzed in 335 patients with documented essential hypertension and 196 control subjects by using PCR-restriction fragment length polymorphism. Expectation maximization(EM) algorithm was then used for pairwise linkage disequilibrium test and haplotype analysis of AGT polymorphisms.
RESULTSLinkage disequilibrium between M235T and A-20C, between M235T and A-6G, between A-20C and A-6G was observed (P<10(-4)). The case-control analysis revealed that the frequency of T235 is significantly higher in essential hypertension patients than in control subjects. But all haplotype frequencies showed no significant difference between the patient and control groups.
CONCLUSIONNo association was noted between the haplotypes of AGT gene and hypertension in tested people, but T235 allele might play an important role in increased risk for essential hypertension.
Alleles ; Angiotensinogen ; genetics ; DNA ; genetics ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Hypertension ; genetics ; Linkage Disequilibrium ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length
6.Study on the association of oral contraceptives, angiotensinogen gene polymorphisms and the risk of stroke in women.
Zhi-zheng HUANG ; Ying LI ; Chun WANG ; Tao SUN ; Hui-qiao LI ; Zhi-ming SUN ; Jian ZHOU ; Lei BA ; Tong CHEN
Chinese Journal of Epidemiology 2013;34(4):321-325
OBJECTIVETo evaluate the associations of oral contraceptives (OC) exposure, angiotensinogen (AGT) gene polymorphism and joint effects on the risk of stroke in Chinese women.
METHODSOn the basis of a prospective female cohort of contraceptive use, the first-ever-developed (FED) stroke cases, as well as, two sets of age-(± 3 years) and region-matched controls (including neighborhoods and hospitalized patients) were recruited. Between 1 July 2000 and 30 June 2009, a total of 453 FED stroke cases and 919 controls were recruited. Genotyping for polymorphisms of AGT gene was detected by Taqman method.
RESULTS(1) The risk of stroke gradually increased with the cumulative time of OC use in women (P < 0.0001). Compared with the non-users, the risk of hemorrhagic stroke slightly increased among those with OC use (OR = 1.83, 95%CI: 1.25 - 2.66). (2) Women with AG/GG genotypes of A-6G locus or CA/AA genotypes of C11535A locus indicated that there was a slightly reduced risk of stroke (OR = 0.78, 95%CI: 0.61 - 0.99; OR = 0.73, 95%CI: 0.56 - 0.95). (3) Women with AA genotypes of A-20C locus and AG/GG genotypes of A-6G, when incorporated with CA/AA genotypes of C11535A locus with OC, it could increase the risk of hemorrhagic stroke (OR = 1.99, 95%CI: 1.34 - 2.97; OR = 1.84, 95%CI: 1.15 - 2.94; OR = 1.73, 95%CI: 1.06 - 2.85).
CONCLUSIONThe AGT gene polymorphisms showed that they did have an impact on the risk of stroke. And the joint effect between women using OC and AGT gene polymorphisms could slightly increase the risk of stroke.
Aged ; Angiotensinogen ; genetics ; Case-Control Studies ; Contraceptives, Oral ; adverse effects ; Female ; Genotype ; Humans ; Middle Aged ; Risk Factors ; Stroke ; etiology ; genetics
7.The association between mutations of 5' upstream core promoter A(-6)G of angiotensinogen gene and liver cirrhosis.
Fan XIAO ; Hong-shan WEI ; Qing-ming DONG ; Wen-mei FAN ; Ya-nan LIU
Chinese Journal of Hepatology 2006;14(8):609-610
Adult
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Angiotensinogen
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genetics
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DNA Mutational Analysis
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Female
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Genome
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Humans
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Liver Cirrhosis
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genetics
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Male
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Middle Aged
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Mutation
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Promoter Regions, Genetic
8.Association of angiotensinogen gene M235T variant with essential hypertension.
Si-yu CAI ; Feng YU ; Yu-ping SHI
Journal of Zhejiang University. Medical sciences 2004;33(2):151-154
OBJECTIVETo investigate the association of the AGT gene M235T variant with essential hypertension in Han population of Zhejiang Province.
METHODSThe study included 230 subjects: 116 hypertensive patients and 114 normotensive controls. Polymerase chain reaction (PCR) combined with restrictive fragment length polymorphism (RFLP) was used to detect the M235T variant of angiotensinogen (AGT) gene. Blood pressure, body height and weight, fasting blood glucose and serum lipid were measured in all subjects.
RESULTS(1)The systolic blood pressure and diastolic blood pressure of hypertensive group were significantly higher than those of control group, while no significant difference was observed with regard to age, gender, body mass index, blood glucose, or lipid profile. (2)The genotype distribution of AGT gene in both groups was in agreement with Hardy-Weinberg equilibrium. (3)The genotype distribution of the M235T variant differed significantly in hypertensives and controls (chi(2)=6.966,P<0.05). The frequencies of genotype TT and T235 allele in hypertensives were higher than those in controls (TT genotype: 0.47 compared with 0.33, chi(2)=5.36,P<0.05; T235 allele: 0.71 compared with 0.60, chi(2)=6.179, P<0.05).
CONCLUSIONThe molecular variant M235T of the AGT gene is significantly associated with essential hypertension in this population. The genotype TT or allele T235 might be a genetic risk factor for hypertension.
Adult ; Aged ; Aged, 80 and over ; Angiotensinogen ; genetics ; Female ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic
9.Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients.
Bedia AGACHAN ; Turgay ISBIR ; Hulya YILMAZ ; Emel AKOGLU
Experimental & Molecular Medicine 2003;35(6):545-549
Essential hypertension is a multifactorial disease in which genetic and enviromental factors play an important role. These factors differ in each population. As there are no existing data for the Turkish population, we investigated four Renin Angiotensin System (RAS) gene polymorphisms, the angiotensin converting enzyme (ACE), angiotensinogen (AGN) M235T/T174M and angiotensin II type 1 receptor A1166C polymorphism in 109 hypertensive and 86 normotensive Turkish subjects. Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to determine these polymorphism. The frequencies of person that carry ACE D allel (DD+ID) was significantly higher in hypertensive group (99.1%) than controls (80%) (P<0.000). M235T TT genotype was also found significantly higher in hypertensives than control group (20% vs 2.7%; P<0.001). The frequency of AGN 174M allele was higher in the hypertensive group than control subjects (8.76% vs 4.81%). Frequency of ATR1 C allele (AC+CC genotypes) was found higher hypertensives than controls (39.4% vs 25.9%; P = 0.054). Our results suggest that an interaction exists between the RAS genes and hypertension in Turkish population.
Angiotensinogen/*genetics
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Female
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Gene Frequency
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Genotype
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Humans
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Hypertension/*genetics
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Male
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Middle Aged
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Peptidyl-Dipeptidase A/*genetics
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Polymorphism, Genetic/*genetics
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Receptor, Angiotensin, Type 1/*genetics
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Renin-Angiotensin System
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Turkey
10.Renin-Angiotensin-Aldosterone System (RAAS) Gene Polymorphism as a Risk Factor of Coronary In-Stent Restenosis.
Sung Kee RYU ; Eun Young CHO ; Hyun Young PARK ; Eun Kyoung IM ; Yangsoo JANG ; Gil Ja SHIN ; Won Heum SHIM ; Seung Yun CHO
Yonsei Medical Journal 2002;43(4):461-472
Intimal proliferation is a main cause of in-stent restenosis. Over-excretion of angiotensin I converting enzyme (ACE) and aldosterone is reported to stimulate intimal hyperplasia and the genetic effect of these molecules may alter the process of in-stent restenosis. We hypothesized that the genetic polymorphisms that alter the expression of genes such as ACE I/D, CYP11B2-344C/T, and AGT M235T can affect in-stent restenosis. We analyzed the angiographic and clinical data of 238 patients (272 stents) who underwent coronary stenting and follow-up angiography, and analyzed the genotypes of ACE I/D, CYP11B2-344T/C, and AGT M235T. There was no significant difference in age, sex, or lipid profiles between the patent and restenosis groups. Diabetes mellitus was more frequent in the binary restenosis group. Quantitative computer-assisted angiographic (QCA) analysis revealed that the risk of in-stent restenosis increased with lesion length and was inversely proportional to post- stenting minimal luminal diameter (MLD) and reference diameter. There was no difference in the frequency of binary restenosis between genotypes in each of the three genes. However, follow-up MLD was significantly smaller in the ACE DD genotype than in the ACE II or ID genotypes. Defining restenosis as MLD 2 mm, the restenosis rate was significantly higher in the ACE DD genotype than in the ACE II or ID genotypes. There was no significant synergistic effect between the three gene polymorphisms. In conclusion, while the ACE I/D polymor phism promoted the progress of in-stent restenosis and was of clinical significance, the other potential variables examined did not correlate with in-stent restenosis.
Adult
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Aged
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Aldosterone Synthase/*genetics
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Angiotensinogen/*genetics
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Coronary Restenosis/*etiology/genetics
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Female
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Genotype
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Human
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Logistic Models
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Male
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Middle Age
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Peptidyl-Dipeptidase A/*genetics
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*Polymorphism (Genetics)
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Risk Factors
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*Stents