Meta-analysis of the ACE gene in ischaemic stroke

The angiotensin-1 converting enzyme (ACE) gene is known to have two polymorphic alleles I/D. People with the DD genotype have been shown to be at greater risk of myocardial infarction, but only in some studies. Similar studies in stroke patients also show inconsistent results, but most of these studies have been underpowered to detect a small contribution to stroke risk from the ACE gene. A meta-analysis was undertaken using all known publications of the ACE polymorphism in ischaemic stroke.

Two computerised databases were searched for all publications relating to case-control studies using the ACE I/D variant in human ischaemic stroke. Seven association studies were identified and a meta-analysis was conducted using the Mantel-Haenszel estimate for odds ratio (OR) to determine whether the DD genotype predicted outcome in either a genetically dominant or recessive model.

1918 white subjects (1196 cases and 722 controls) were used in the meta-analysis. There was no difference in ACE genotype (chi2=2.92, p>0.05) or I/D allele frequency (chi2=3.28, p>0.05) in cases or controls. The overall OR for the D allele as an independent risk factor in ischaemic stroke was 1.31 (95% confidence interval (95% CI): 1.06-1.62, p=0.01) under a recessive model, and 1.14 (95% CI: 0.91-1.44, p=0.26) under a dominant model.

This meta-analysis shows that the the D allele, acting recessively, is a modest but independent risk factor for ischaemic stroke onset. Meta-analysis may usefully be employed in allelic association studies for detecting small attributable risks of candidate genes in polygenic disorders.