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

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.