Angiotensinogen T174M and M235T gene polymorphisms are associated with the extent of coronary atherosclerosis

Gardemann, Andreas; Stricker, Jürgen; Humme, Jörg; Nguyên, Quôc Dinh; Katz, Norbert; Philipp, Monika; Tillmanns, Harald; Hehrlein, F. W.; Haberbosch, Werner

doi:10.1016/s0021-9150(99)00082-9

Cited by 61 publications

(37 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although some studies support our results, 4,6 others failed to show such an association. 7,8 Several possible factors may contribute to these discrepancies such as the genetic and environmental heterogeneity among the different ethnic groups. 15 Interestingly, we found that hypertension was the most important risk factor for AMI in our population.…”

Section: Discussionmentioning

confidence: 99%

Angiotensinogen gene polymorphism in acute myocardial infarction patients

Mehri¹,

Mahjoub²,

Farhati

et al. 2010

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

Introduction. The objective of the study was to explore the role of a genetic variant of angiotensinogen (AGT), M235T, as an independent risk factor for acute myocardial infarction (AMI) and to investigate the possible association with the severity of coronary artery disease (CAD), estimated on the basis of the number of coronary stenoses and critical arterial occlusions. Patients and methods. 123 AMI patients were compared to 144 healthy controls. AGT genotypes were determined by PCR. Results. A significant association was found between AGT M235T polymorphism and AMI (p = .021). By logistic regression, the TT genotype appeared to confer 1.9-fold increased risk for AMI in both the univariate and the multivariate model. The frequencies of the TT genotype and T allele increased with the number of stenoses in coronary vessels. Moreover, the TT genotype and the T allele were more frequent in the subgroup of patients with stenoses in at least four coronary vessels than in other patients, including subjects with one-to three-vessel disease. Furthermore, the TT genotype and the T allele were significantly more frequent in patients with critical arterial occlusions (> 90%) than in subjects without critical stenoses. Conclusions. The AGT M235T polymorphism associates with AMI risk and influences CAD severity.

show abstract

Section: Discussionmentioning

confidence: 99%

Angiotensinogen gene polymorphism in acute myocardial infarction patients

Mehri¹,

Mahjoub²,

Farhati

et al. 2010

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

show abstract

“…Moreover, because the type 1 diabetic population from the study of van Ittersum et al had significantly shorter disease duration (17.1 Ϯ 11.4 years) in comparison with our cohort (23.5 Ϯ 9 years at baseline) and had a limited number of cardiovascular events (38 of 257), it is also possible that their study did not have sufficient power to detect differences in CAD risk between the carriers of different RAS genotypes or genotypes combinations. In fact, there is increasing evidence that the T235 variant is associated with myocardial infarction and other forms of clinically overt coronary heart disease in the general population (17,40). Recently, the RAS has been thought to play a critical role also in the development of CACs (41).…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of the Renin-Angiotensin System Genes Predict Progression of Subclinical Coronary Atherosclerosis

Krętowski

McFann

Hokanson³

et al. 2007

Diabetes

View full text Add to dashboard Cite

Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5-29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6 -388], P ‫؍‬ 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes. Diabetes 56:863-871, 2007 P atients with type 1 diabetes have a dramatically higher risk of coronary artery disease (CAD) compared with the general population (1,2). Coronary artery calcification (CAC), a marker of coronary artery plaque burden, correlates very well with the established CAD risk factor profile in patients with type 1 diabetes (3-5). There is growing evidence that CAC strongly predicts future coronary events in asymptomatic nondiabetic and diabetic subjects (4 -6).Diabetic nephropathy plays an important role in the pathogenesis of advanced CAD in type 1 diabetes (2). However, little is known concerning determinants of subclinical atherosclerosis detected as rapidly progressing CAC. Activation of the renin-angiotensin system (RAS) by hyperglycemia may be the key mechanism (7,8). The RAS involves enzymatic processing of angiotensinogen (AGT) to angiotensin I, further cleaved by ACE to angiotensin II. Treatment with ACE inhibitors lowers the risk of cardiovascular death, myocardial infarction, and coronary revascularization in the general population and in diabetic patients (9 -11).The RAS activity is modified by variants of the genes coding functional proteins of this pathway (12-14). The AGT gene, localized on chromosome 1q41-qter, encodes AGT. There is only one haplotype block at the AGT locus, and all common single nucleotide polymorphisms (SNPs) identified appear to be in complete linkage disequilibrium with the most intensively studied M235T polymorphism (13,15). Although the functional variant has not yet been definitively identified (16), the T235 allele has been consistently associated with cardiovascular disease (13,17) and ...

show abstract

“…Relevant clinical outcome included confirmed myocardial infarction (generally by World Health Organization criteria) and coronary stenosis (defined variously as at least 50% 10,11,13,17,18,20,27,31,34,36,37,39,41,45,48,50 or 70% 9,12,23 stenosis of Ն1 major coronary arteries on the basis of computerassisted assessments). For the M235T polymorphism, sufficient data existed to analyze these outcomes separately.…”

Section: Data Extractionmentioning

confidence: 99%

“…Of the remaining studies, 2 used oligonucleotide probes, 9,10 2 used single-tube bidirectional allele-specific amplification, 33 Figure 2) and for coronary stenosis of 1.13 (95% CI, 1.04 to Figure 4). Analysis restricted to the 4 studies 6,20,29,47 with at least 500 cases (total, 6760 cases and 9959 controls), which should be less prone to selective publication than smaller studies, yielded an OR of 5 9 9 1 , t e r i T 3 0 0 2 , s i B 0 0 0 2 , a l l a t a B 4 0 0 2 , h t i j n a R 0 0 0 2 , a v e h c i m o F 9 9 9 1 , s a c r A -z e d n a n r e F 2 0 …”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Quantitative Assessment of the Effect of Angiotensinogen Gene Polymorphisms on the Risk of Coronary Heart Disease

Zheng

et al. 2007

Circulation

View full text Add to dashboard Cite

Background-Angiotensinogen, a key protein in the renin-angiotensin system, plays an important role in cardiovascular hemostasis. Many studies have examined the association between polymorphisms in the angiotensinogen gene and risk of coronary heart disease (CHD), but the results have been inconsistent. Methods and Results-We performed a meta-analysis of 43 associations studies on 2 angiotensinogen polymorphisms (M235T and T174M) and risk of CHD published before March 2007, including a total of 13 478 CHD cases and 17 024 controls. We also explored potential sources of heterogeneity. In a combined analysis, the summary per-allele odds ratio for CHD of the M235T polymorphism was 1.11 (95% confidence interval, 1.03 to 1.19). However, when the analyses were restricted to 4 larger studies (n Ͼ500 cases), the summary per-allele odds ratio was 0.99 (95% confidence interval, 0.94 to 1.04). Our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. A meta-analysis of studies on the 174M variant showed no significant overall association with CHD, yielding a per-allele odds ratio of 1.07 (95% confidence interval, 0.93 to 1.22). Conclusions-This meta-analysis suggested an overall weak association between the M235T polymorphism and CHD risk.However, the association was not observed in several larger studies, suggesting a publication bias. Additional very large-scale studies are warranted to provide conclusive evidence on the effects of the angiotensinogen gene and other genes within the renin-angiotensin system on risk of CHD.

show abstract

Angiotensinogen T174M and M235T gene polymorphisms are associated with the extent of coronary atherosclerosis

Cited by 61 publications

References 25 publications

Angiotensinogen gene polymorphism in acute myocardial infarction patients

Angiotensinogen gene polymorphism in acute myocardial infarction patients

Polymorphisms of the Renin-Angiotensin System Genes Predict Progression of Subclinical Coronary Atherosclerosis

Quantitative Assessment of the Effect of Angiotensinogen Gene Polymorphisms on the Risk of Coronary Heart Disease

Contact Info

Product

Resources

About