Association of angiotensin-converting enzyme insertion/deletion polymorphism (rs4646994) with the risk of primary intracerebral hemorrhage

Abstract

Background: Evidence has suggested that angiotensin-converting enzyme (ACE) may be involved in the etiology of primary intracerebral hemorrhage (PICH), but the underlying association between ACE I/D (rs4646994) polymorphism and PICH risk is still ambiguous. This meta-analysis was performed to quantitatively summarize the evidence for such a relationship.

Methods: Eligible studies were identified by searching PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBM (Chinese biomedical literature database), and WANFANG databases within a range of published years from 1990 to August 2012. The odds ratio (OR) corresponding to the 95% confidence interval (CI) was used to assess the different associations.

Results: A total of 28 studies with 2806 cases and 3612 controls were included in this meta-analysis. The pooled examination displayed an overall increased PICH risk associated with ACE I/D polymorphism in a recessive model (OR  =  1·80, 95% CI  =  1·39–2·33, P < 0·001 for DD versus ID/II), however, this association was only present in Asians (OR  =  1·91, 95% CI  =  1·45–2·51, P < 0·001) and not in Caucasians (OR  =  1·16, 95% CI  =  0·55–2·44, P  =  0·69). Hypertensive intracerebral hemorrhage (HICH) had a much greater risk (OR  =  4·26, 95% CI  =  2·87–6·32, P < 0·001) than general PICH (OR  =  1·65, 95% CI  =  1·25–2·18, P < 0·001) in Asians, and subgroup with controls excluding hypertension had a greater risk (OR  =  2·65, 95% CI  =  1·78–3·95, P < 0·001) than that including hypertension (OR  =  1·50, 95% CI  =  1·12–2·02, P  =  0·01).

Conclusions: This meta-analysis suggests that DD homozygote of ACE I/D polymorphism has an increased PICH risk in Asians, and may have a synergistic effect with hypertension.

Keywords:

• Cerebral hemorrhage
• Hemorrhagic stroke
• Angiotensin-converting enzyme
• Polymorphism
• Meta-analysis