Angiotensin Converting Enzyme (ACE) Gene I/D Polymorphism Is Significantly Associated with Insulin Resistance and Polycystic Ovary Syndrome: A Meta-Analysis

Introduction: This study was performed to clarify the effects of angiotensin converting enzyme (ACE) I/D polymorphism on the risk of insulin resistance and polycystic ovary syndrome (PCOS).

Methods: Six genotype models and the mean difference (MD)/standardized mean difference (SMD) were applied to evaluate the effects of ACE I/D polymorphism on insulin resistance and PCOS risk.

Results: Thirteen studies with 3,212 PCOS patients and 2,314 controls were collected. In the pooled analysis and Caucasian subgroup, the ACE I/D polymorphism was significantly associated with PCOS risk, even after removing the non-Hardy-Weinberg equilibrium (HWE) studies. Moreover, the positive effect of ACE I/D polymorphism in PCOS was mainly presented in Caucasians (removing non-HWE, DD + DI vs. II: odds ratio [OR] = 2.15, p = 0.017; DD vs. DI + II: OR = 2.64, p = 0.007; DD vs. DI: OR = 2.48, p = 0.014; DD vs. II: OR = 3.31, p = 0.005; D vs. I: OR = 2.02, p = 0.005) compared to Asians. Interestingly, only in Asians was the ACE I/D polymorphism significantly correlated to insulin levels (DI vs. II: SMD = 0.19, 95% CI = (0.03, 0.35), p = 0.023) and HOMA-IR (DI vs. II: MD = 0.50, 95% CI = (0.05, 0.95), p = 0.031).

Conclusions: The D allele of the ACE I/D polymorphism promotes PCOS development. Moreover, the ACE I/D polymorphism was also associated with insulin-resistant PCOS, especially among Asians.