A1166C genetic variation of the angiotensin II type I receptor gene and susceptibility to coronary heart disease: Collaborative of 53 studies with 20,435 cases and 23,674 controls

Xu, Mingqing; Sham, Pak; Ye, Zheng; Lindpaintner, Klaus; He, Lin

doi:10.1016/j.atherosclerosis.2010.07.046

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Volume 213, Issue 1 , Pages 191-199, November 2010

A1166C genetic variation of the angiotensin II type I receptor gene and susceptibility to coronary heart disease: Collaborative of 53 studies with 20,435 cases and 23,674 controls

Mingqing Xu
- Brigham and Women's Hospital, School of Medicine, Harvard University, Boston, MA 02115, USA
- School of Public Health, Harvard University, 665 Huntington Avenue, Boston, MA 02115, USA
- Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China
- Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China
- Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
- Corresponding author at: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China; Brigham and Women's Hospital, School of Medicine, Harvard University, Boston, MA 02115, USA. Tel.: +1 6174322984; fax: +16174322984.
Pak Sham
- HKU Department of Psychiatry and Genome Research Centre, University of Hong Kong, Pokfulam Road, Hong Kong, PR China
Zheng Ye
- Department of Public Health and Primary Care, University of Cambridge, Strangeways Site, Worts Causeway, Cambridge CB1 8RN, UK
Klaus Lindpaintner
- Roche Center for Medical Genomics, F. Hoffmann-La Roche, Ltd., Basel, Switzerland
Lin He
- Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China
- Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China
- Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
- Corresponding author at: Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China; Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China. Tel.: +862162822491; fax: +862162822491.

Received 2 February 2010; received in revised form 19 July 2010; accepted 20 July 2010. published online 23 August 2010.

Abstract

Objective

Angiotensin II induces vasoconstriction and vascular smooth muscle growth via stimulation of the angiotensin II type I receptor (AGTR1). Some studies have reported an association between a genetic variant (A1166C) in the 3′ un-translated region of AGTR1 and increased risk of coronary heart disease (CHD), but other have yielded apparently conflicting results.

Methods

Literature-based meta-analyses were performed on 48 papers including 53 studies published before June 2008 in relation to the A1166C polymorphism (NCBI, dbSNP: rs5186) of the AGTR1, involving a total of 20,435 CHD cases and 23,674 controls. We also explored potential sources of heterogeneity and conducted appropriate stratified analyses.

Results

In a combined analysis, the per-allele odds ratio (OR) for CHD of the A1166C polymorphism was 1.11 (95% confidence interval: 1.03–1.19), but there is an indication of publication bias and heterogeneity among the 53 studies. Sample size and study quality were significant sources of heterogeneity among studies of the A1166C polymorphism with possibly overestimates in studies of smaller sample-size and poor-quality. When the analyses were restricted to 11 larger studies (≥500 cases), and to 8 high-quality studies (quality score: ≥11 points), the summary per-allele odds ratios were 0.992 (95% confidence interval, 0.944–1.042) and 0.990 (95% confidence interval, 0.915–1.072), respectively.

Conclusions

An overall weak association between the A1166C polymorphism and CHD is observed but this is likely to be due to publication bias and heterogeneity between studies. There were no significant associations among the larger sample-size and high-quality studies which are less prone to selective publication and have greater power to detect a true association.

Keywords: Angiotensin II type I receptor gene, Coronary heart disease, Genetic polymorphism