Angiotensin-converting enzyme gene deletion allele increases the risk of left ventricular hypertrophy: evidence from a meta-analysis

Abstract

Large panels of studies have examined the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk for left ventricular hypertrophy (LVH), yet with inconclusive results. We therefore sought to evaluate this association via a comprehensive meta-analysis. A random-effects model was applied irrespective of between-study heterogeneity. Data and study quality were independently assessed by two investigators. Total 52 studies encompassing 3,663 case-patients and 8,953 controls were meta-analyzed. Overall results indicated that carriers homozygous for DD genotype conferred 1.59 times (95 % confidence interval [95 % CI]: 1.31-1.92; P < 0.0005) more likely to develop LVH compared with those with II genotype, accompanying moderate evidence of heterogeneity (I (2) = 49.0 %). In subgroup analyses by ethnicity, DD homozygotes had a 90 % (95 % CI: 1.42-2.53; P < 0.0005) increased risk in East Asians, but merely a 33 % (95 % CI: 1.03-1.73; P = 0.032) increased risk in Caucasians. Moreover, differences in source of controls, cutoff for the definition of hypertension, and diagnostic method of LVH were also regarded as potential sources of heterogeneity. Further, the risk estimate associated with D allele was more pronounced in studies involving males (odds ratio [OR] = 1.47; 95 % CI: 1.2-1.8; P < 0.0005) and untreated subjects (OR = 1.39; 95 % CI: 1.2-1.62; P < 0.0005). The magnitude of publication bias was greatly improved in homozygous subgroups. Taken together, our results demonstrated significant association of ACE gene I/D polymorphism with LVH risk, especially in East Asians, and this association was more pronounced in studies involving males and untreated subjects.