Relationship Between Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism and Systemic Lupus Erythematosus/Lupus Nephritis: A Systematic Review and Metaanalysis

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. (First Release Feb 15 2012; J Rheumatol 2012;39:686-93; doi:10.3899/jrheum.110863)