Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes High Risk for Chronic Kidney Disease in Asian Male with Hypertension-A Meta-Regression Analysis of 98 Observational Studies

Background: Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial. Objectives: This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk. Data sources: PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013. Study eligibility criteria, participants, and interventions: Cross-sectional surveys and case-control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity. Study appraisal and synthesis methods: The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models. Results: Ethnicity [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.08-1.42] and hypertension (OR: 1.55; 95% CI: 1.04-2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p<0.05). In subgroup analyses, this result was significant in the nondiabetic nephropathy group. Compared with the I allele, the D allele had the highest risk (OR: 3.75; 95% CI: 1.84-7.65) for CKD in hypertensive Asian males. Conclusions and implications of key findings: The ACE I/D polymorphisms may incur the highest risk for increasing CKD in hypertensive Asian males.