Published Online
on September 10, 2007

A more recent version of this article appeared on September 18, 2007

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Submitted on April 9, 2007
Accepted on July 23, 2007

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

Ming-Qing Xu PhD^*, Zheng Ye PhD, Frank B. Hu MD, PhD, and Lin He PhD^*

From the Bio-X Life Science Research Centre, Shanghai Jiao Tong University, Shanghai, China (M.-Q.X., L.H.); Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (M.-Q.X., L.H.); School of Public Health, Harvard University, Boston, Mass (M.-Q.X., F.B.H.); Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (F.B.H.); and Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK (Z.Y.).

^* To whom correspondence should be addressed. E-mail: mxu{at}hsph.harvard.edu or helin{at}bio-x.cn.

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 >500 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.

Key words: angiotensinogen • coronary disease • genetics • haplotypes • linkage disequilibrium • myocardial infarction • risk factor

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