PLoS ONE (Jan 2014)

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.

  • Chin Lin,
  • Hsin-Yi Yang,
  • Chia-Chao Wu,
  • Herng-Sheng Lee,
  • Yuh-Feng Lin,
  • Kuo-Cheng Lu,
  • Chi-Ming Chu,
  • Fu-Huang Lin,
  • Sen-Yeong Kao,
  • Sui-Lung Su

DOI
https://doi.org/10.1371/journal.pone.0087604
Journal volume & issue
Vol. 9, no. 1
p. e87604

Abstract

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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.