Relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and systemic lupus erythematosus/lupus nephritis: a systematic review and metaanalysis

J Rheumatol. 2012 Apr;39(4):686-93. doi: 10.3899/jrheum.110863. Epub 2012 Feb 15.

Abstract

Objective: Results from studies of the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and systemic lupus erythematosus (SLE)/lupus nephritis (LN) are controversial. We performed this metaanalysis to evaluate the relationship between ACE I/D gene polymorphism and SLE/LN and to explore whether the ACE D allele or DD genotype could become a predictive marker for risk of SLE/LN.

Methods: Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of May 1, 2011, and eligible investigations were synthesized using a metaanalysis method. Results were expressed with OR for dichotomous data, and 95% CI were calculated.

Results: Sixteen investigations were identified for the analysis of association between ACE I/D gene polymorphism and SLE, consisting of 1959 patients with SLE and 2078 controls. In the overall populations, there was a marked association between D allele or DD genotype and SLE susceptibility (D: OR 1.29, 95% CI 1.04-1.58, p = 0.02; DD: OR 1.60, 95% CI 1.17-2.19, p = 0.003), and DD homozygous was associated with LN risk (OR 2.78, 95% CI 1.26-6.11, p = 0.01). In the subgroup analysis, DD genotype associated with SLE risk was observed in Asians; no other association was found in Asians, whites, Africans, and Brazilians.

Conclusion: D allele and DD homozygous are significant genetic molecular markers to predict SLE susceptibility, and DD genotype is a valuable marker to predict the LN risk. More investigations are required to clarify the association of the D allele or DD homozygous with SLE/LN susceptibility.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • INDEL Mutation / genetics*
  • Lupus Erythematosus, Systemic / enzymology
  • Lupus Erythematosus, Systemic / epidemiology*
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Nephritis / enzymology
  • Lupus Nephritis / epidemiology*
  • Lupus Nephritis / genetics*
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic / genetics
  • Risk Factors

Substances

  • ACE protein, human
  • Peptidyl-Dipeptidase A