Association of AGT M235T and ACE I/D polymorphisms with the risk of ischemic stroke: meta-analysis in Han Chinese population

Background: Angiotensinogen (AGT) M235T and angiotensin-converting enzyme (ACE) Insertion/Deletion polymorphisms have been reported to be significantly associated with ischemic stroke. However, the results have been inconsistent. Therefore, we performed a comprehensive meta-analysis to evaluate the role of the AGT M235T and ACE I/D polymorphisms as risk factors for ischemic stroke in Han Chinese population.

Methods: We performed a comprehensive search in MEDLINE (PubMed), the China National Knowledge Infrastructure (CNKI) platforms and WANFANG databases, to identify the studies evaluating the association between the AGT M235T or ACE I/D polymorphisms and ischemic stroke, up to August 2011, in Chinese and English languages. The combined effects were estimated by fixed effects model or random effects model depending on the between-study heterogeneity, which was analyzed using the heterogeneity Q statistic test. Publication bias was evaluated using Begg's test, Egger's test and funnel plot.

Results: A total of 58 studies were selected for the final meta-analysis, including 7168 ischemic stroke cases and 5944 controls. Among them, 11 studies evaluated the effect of AGT M235T as a risk factor for ischemic stroke, while the remaining evaluated the ACE I/D polymorphism. Overall, a significant association was identified for both the AGT M235T and ACE I/D polymorphisms, under pair wise comparisons, dominant, recessive and additive models, however, there was significant heterogeneity among the ACE I/D polymorphism studies (P<0.10). On meta-regression analyses, geographic region was identified as a significant source of between-study heterogeneity for both the polymorphisms. The stratified analysis by geographic distribution indicated that the AGT T allele could increase the risk of ischemic stroke in northern Chinese (OR=2.029, 95% CI: 1.714-2.401, P<0.001) as compared to southern Chinese individuals (OR=1.821, 95% CI: 1.586-2.090, P=0.002). In contrast, the ACE D allele could increase the susceptibility of ischemic stroke in southern Chinese (OR=1.692, 95% CI: 1.455-1.966, P<0.001) as compared to northern Chinese individuals (OR=1.297, 95% CI: 1.089-1.545, P=0.004). There was a possibility of publication bias for ACE I/D (P<0.001), but not for AGT M235T (P>0.05).

Conclusions: Our meta-analysis strongly suggested that the AGT M235T and ACE I/D polymorphisms significantly contribute to the risk of ischemic stroke in Han Chinese population. Also, the stratified analysis showed that the effects of these two polymorphisms differ by the geographic region. Further studies with more specific common information and large sample size are needed to understand the genetic mechanism of ischemic stroke.