Angiotensinogen M235T polymorphism is associated with coronary artery disease severity (original) (raw)
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Erciyes Medical Journal, 2021
Objective: Coronary artery disease (CAD) is a multifactorial disorder and is caused by both environmental and genetic factors. As the alterations in angiotensinogen (AGT) gene lead to changes in angiotensin II and plasma levels of AGT, variants of this gene may play a role in CAD pathogenesis. This study aimed to investigate the relationship between CAD and polymorphisms of AGT gene at M235T and T174M regions. Moreover, the associations of potential risk factors with these gene regions and CAD were investigated. Materials and Methods: In total, the study enrolled 214 cases with CAD and 200 controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to detect polymorphisms at M235T and T174M. PCR products were electrophoresed on 2% agarose gel, with ethidium bromide, and were then examined under ultraviolet light. Subsequently, RFLP was used to detect gene polymorphisms. A multiple binary logistic regression model was used to investigate the association of risk factors with both CAD and AGT variants. Results: The number of TT polymorphisms at M235T were significantly higher in the case group than in control group. However, there were no significant differences between cases and controls regarding T174M gene polymorphisms. The presence of hypertension, low high-density lipoprotein level, alcohol consumption, and family history were associated with CAD. Conclusion: TT polymorphisms at the M235T region in AGT can be an influential factor in the development of CAD.
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Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease
The Lancet, 1995
Several genes, including some encoding components of the renin angiotensin system, are associated with the risk of cardiovascular diseases. There have been reports linking a homozygous deletion allele of the angiotensin converting enzyme (ACE) gene (DD) with an increased risk of myocardial infarction, and some variants of the angiotensinogen gene with an increased risk of hypertension. In a case-control study of a caucasian population from New Zealand, we examined the associations with coronary heart disease (CHD) of ACE DD and of a mis-sense mutation with methionine to threonine aminoacid substitution at codon 235 in the angiotensinogen gene (T235). We studied 422 patients (mean age 62 years, 81% male) with documented CHD (50% with myocardial infarction) and 406 controls without known CHD (frequency-matched to cases by age and sex). Risk factors for CHD were assessed by standard questionnaire, physical examination, and blood tests. Genomic DNA from leucocytes was analysed for various ACE and angiotensinogen alleles. Angiotensinogen T235 homozygotes were at significantly increased risk of CHD generally (odds ratio 1.7, 2 p = 0.008) and of myocardial infarction specifically (1.8, 2 p = 0.009). Adjustment for several risk factors increased the estimate of CHD risk associated with this allele to 2.6 (2 p < 0.001) and the estimate for myocardial infarction risk to 3.4 (2 p < 0.001). By contrast, there was no evidence of a significant increase in the risk of CHD or myocardial infarction among individuals with ACE DD. We conclude that the T235 polymorphism of the angiotensinogen gene is an independent risk factor, which carries an approximately two-fold increased risk of CHD. In this study, however, ACE DD was not associated with any detectable increase in CHD risk.
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Human Genetics, 1996
Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with coronary artery disease (CAD) but no relation between these polymorphisms and coronary atherosclerosis has yet been systematically evaluated. The CORGENE study is a cross-sectional study involving 463 Caucasians who underwent standardized coronary angiography for established or suspected CAD [156 patients with a previous myocardial infarction (MI), 307 without MI]. Four angiographic scores assessing the extent and severity of the coronary lesions were obtained from a double visual analysis of each angiogram, arbitration being achieved by a quantitative measurement. Three different genotypes were analyzed: the angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism, the Met to Thr change at position 235 of the angiotensinogen gene (AGT M235T) and the A to C transition at position 1166 of the angiotensin II type-1 receptor gene (AT1R A1166C). No significant association was observed between these polymorphisms and the clinical characteristics of MI and non-MI subjects. While most classical risk factors were positively correlated with the angiographic scores, no significant relationship could be established with the three genotypes (r ranging from –0.08 to 0.05). Only one significant correlation was observed: between the presence of the AGT 235T allele and the extent of the coronary lesions (r = –0.19, P = 0.04) in patients with low-risk status. These overall results are not in favor of a role of these RAS genetic polymorphisms in the development of coronary atherosclerosis.
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Croatian medical journal, 2016
To investigate if there is an association between M235T polymorphism of angiotensinogen gene and myocardial infarction (MI) risk and perform a meta-analysis and an in silico approach. This case-control study included 340 participants (155 MI patients and 185 controls) examined at Kashan University of Medical Sciences (Kashan, Iran) between 2013 and 2015. Meta-analysis included 25 studies with 6334 MI patients and 6711 controls. Bioinformatics tools were applied to evaluate the impact of M235T polymorphism on angiotensinogen function and structure. Genetic association study revealed a significant association between TT genotype (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.08-4.00, P=0.029) and T allele (OR 1.45, 95% CI 1.06-1.99, P=0.021) and MI risk. Meta-analysis also revealed a significant association between M235T polymorphism and MI risk in allelic (OR 1.55, 95% CI 1.10-2.18, P=0.012) and recessive (OR 1.69, 95% CI 1.13-2.53, P=0.010) models within Asian population. In ...
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2021
Coronary artery disease (CAD) is a multifactorial disease that involves genetic and environmental interaction. In addition to the well-known CAD risk factors, such as diabetes mellitus, hypertension, hyperlipidemia, and atherosclerosis, it has a genetic component that predisposes to its occurrence even in young people. One of the most commonly studied genes that increase the susceptibility to CAD is renin-angiotensin system (RAS) genes polymorphisms mainly angiotensin-converting enzyme gene (ACE) polymorphisms, angiotensinogen polymorphisms, angiotensin- II type 1 receptor gene polymorphisms, and many other genes. These genetic polymorphisms have a direct association with CAD development or indirect association through causing atherosclerosis and hypertension which, in turn, are complicated by CAD later on. The difference between genetic mutations and polymorphisms lies in the frequency of the abnormal genotype. If the frequency is 1% and more in the general population, it is called...
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