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Angiotensin II plays an important role in the regulation of blood pressure and vascular homeostasis. However, over-production 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 [3–17], 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: ‘angiotensin type 1 receptor’ or ‘AT1R’ or ‘AGT1R’, ‘polymorphism’ or ‘single nucleotide polymorphism’ or ‘SNP’, and ‘myocardial infarction’. 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 [3,4,6–11,13–20].

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).

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Figure 1.  Meta-analysis of AT1R gene A1166C polymorphism variant genotypes and their association with risk of myocardial infarction. (A) CC vs. AA; (B) AC/CC vs. AA. The study by Su et al. [13] was excluded due to deviation from Hardy–Weinberg equilibrium and association recalculated: (C) CC vs. AA; (D) AC/CC vs. AA.

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The results of this meta-analysis suggest that the C allele of the AT1R gene A1166C polymorphism is associated with an increased risk of MI. However, we cannot infer a causal relationship between the AT1R genotype and the risk of MI by this cross-sectional analysis, and we cannot clarify the inner mechanisms by which the AT1R genotype increases MI risk. Further larger, muticentre, prospective studies are necessary to establish a causal link between the AT1R genotype and MI. In addition, systematic evaluation of the interaction of AT1R and other related genes might further interpret the internal mechanisms of vascular pathophysiological processes.

In conclusion, our study indicates an association of the C allele of AT1R gene A1166C polymorphisms and MI. Further investigations are needed to illuminate the possible mechanisms involved in this phenomenon.

Disclosure of Conflict of Interests

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The authors state that they have no conflict of interest.

References

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  2. Disclosure of Conflict of Interests
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