Association of the angiotensin type 1 receptor gene A1166C polymorphisms with myocardial infarction: a meta‐analysis

Abstract

Angiotensin II plays an important role in the regulation of blood pressure and vascular homeostasis. However, overproduction of angiotensin II leads to multiple and diverse effects, including hypertension and atherosclerosis. All the above effects are mostly mediated by the angiotensin type 1 receptor (AT1R) [1]. The AT1R gene A1166C polymorphism has been considered an important factor in the risk of myocardial infarction (MI). In 1994, Tiret et al.[2] first reported the C-allele distribution in both MI cases and controls. Since then, studies both supporting and questioning this association have been published [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], leading to uncertainty about the importance of this polymorphism. The aim of this study was to assess the association of the AT1R gene A1166C polymorphism and MI by performing a meta-analysis.We searched studies published in English using Medline (from 1966 to March 2011) and the following keywords: Ôangiotensin type 1 receptorÕ or ÔAT1RÕ or ÔAGT1RÕ, ÔpolymorphismÕ or Ôsingle nucleotide polymorphismÕ or ÔSNPÕ, and Ômyocardial infarctionÕ. References in retrieved articles were also searched. The inclusion criteria were as follows: (i) based on a case-control design; (ii) evaluation of the association of MI and A1166C polymorphism; and (iii) available genotype frequency. For studies with overlapping subjects, those with larger sample size were included. Two reviewers (H. Zhang and M. L. Sun) independently searched the articles and extracted information. Discrepancies were resolved, through discussion, by a third reviewer (J. Peng). The analyses were performed with the REVIEWER MANAGER 5.0.25 package (The Cochrane Collaboration, Oxford, UK).A total of 95 abstracts were identified. Of those, 19 studies were retrieved for more detailed evaluation. Three articles were excluded due to duplication of data [2,5,12]. Sixteen studies fulfilled the inclusion criteria and were selected for further data analysis [3,4,[6][7][8][9][10][11][13][14][15][16][17][18][19][20].In total, 6194 cases and 5716 controls were included from 16 studies. The overall distribution of genotypes in the controls was 57.3% AA, 35.9% AC and 6.8% CC, respectively. Compared with the AT1R AA genotype, subjects with the CC genotype showed a significantly higher risk of MI (odds ratio (OR) = 1.35; 95% confidence interval (CI), 1.05-1.73; P = 0.02) (Fig. 1A). Due to the low frequency of the CC genotype, we further compared the C allele carriers (AC/CC) with the AA genotype, which also revealed that individuals with the AC or CC genotype were more susceptible to MI (OR = 1.17; 95% CI, 1.04-1.31; P = 0.008) (Fig. 1B). Considering the deviation from Hardy-Weinberg equilibrium, we removed the study by Su et al. [13]. However, the pooled OR was not appreciably altered (CC vs. AA: OR = 1.38; 95% CI, 1.08-1.76; P = 0.01; AC/CC vs. AA: OR = 1.18; 95% CI, 1.05-1.33; P = 0.007) (Fig. 1C,D).The results of this meta-analysis suggest that the C allele of the AT1R gene A1166C polymorphism is associated with a...

A systematic review and meta-analysis of the association between angiotensin II type 1 receptor A1166C gene polymorphism and myocardial infarction susceptibility

“…Further studies in Africans, the Durban population, and the Brazilian population should be performed. Interestingly, Zhang et al 9 performed the first metaanalysis to study the association of the AT1R gene A1166C polymorphisms with MI risk, and found an association of the C allele of AT1R gene A1166C polymorphisms with MI risk in overall populations. It was similar with our result in this meta-analysis.…”

“…7 The AT1R is present predominantly in vascular smooth muscle cells and because of the physiological role of the AT1R in the cardiovascular system, the gene that encodes this molecule is an excellent candidate in the etiology of cardiovascular diseases 8 AT1R A1166C gene polymorphism, an important mutation of AT1R, might be implicated in the etiology of MI susceptibility and had been investigated in numerous epidemiologic studies. Zhang et al 9 performed the first meta-analysis to study the association of the AT1R gene A1166C polymorphisms with MI risk, and found an association of the C allele of AT1R gene A1166C polymorphisms with MI risk. This meta-analysis was performed to update the conclusion of the relationship between AT1R A1166C gene polymorphism and MI susceptibility, with the intention to provide a much more reliable finding of the significance of this association.…”

Effect of rs4646994 polymorphism of angiotensin-converting enzyme on the risk of nonischemic cardiomyopathy

“…Polymorphisms in the ACE gene, encoding one of the components of the renin–angiotensin–aldosterone system (RAAS), have been found to be associated with a variety of cardiovascular diseases, such as hypertension, myocardial infarction, and cardiomyopathy [ 39 , 40 ]. Increased synthesis of angiotensin II induces cell proliferation, migration, and hypertrophy and can enhance proinflammatory cytokine and matrix metalloproteinase production.…”

Association study of angiotensin II type 1 receptor: A1166C (rs5186) polymorphism with coronary heart disease using systematic meta-analysis

“…Previous meta-analysis conducted by Zhang suggests that the C allele of AT1R-A1166C polymorphism is associated with an increased risk of myocardial infarction (MI). 49 Xu et al conducted a meta-analysis, and their results suggest that AT1R-A1166C polymorphism was associated with increased CHD risk in the overall analysis. However, null result was found in the East Asia population in an analysis by geographic region.…”