Meta-analysis of the Relationship Between ACE I/D Gene Polymorphism and End-Stage Renal Disease in Patients With Diabetic Nephropathy

Nephrology (Carlton). 2012 Jul;17(5):480-7. doi: 10.1111/j.1440-1797.2012.01592.x.


Aims: Diabetic nephropathy (DN) is the major cause for end-stage renal disease (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present. Results from published studies on the relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN patients are still conflicting. This meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD risk in DN patients.

Methods: Association studies were identified from the databases of PubMed, Embase and Cochrane Library on 1 October 2011, and eligible investigations were identified and synthesized using the meta-analysis method. Results were expressed using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI) were also calculated.

Results: Twelve studies reporting the relation between ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In overall populations, there was a notable association between D allele or DD genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11-1.56, P = 0.002; DD: OR = 1.67, 95% CI: 1.25-2.21, P = 0.0004). In the sub-group analysis according to ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In Caucasians, the association of DD genotype with ESRD risk was observed, but the D allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD risk in patients with DN due to diabetes mellitus type 2, but the association was not found for patients with DN due to diabetes mellitus type-1.

Conclusions: Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / enzymology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetic Nephropathies / enzymology
  • Diabetic Nephropathies / ethnology
  • Diabetic Nephropathies / genetics*
  • Disease Progression
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Kidney Failure, Chronic / enzymology
  • Kidney Failure, Chronic / ethnology
  • Kidney Failure, Chronic / genetics*
  • Odds Ratio
  • Peptidyl-Dipeptidase A / genetics*
  • Phenotype
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors


  • ACE protein, human
  • Peptidyl-Dipeptidase A