Angiotensin-Converting Enzyme Gene I/D Polymorphism Is Associated With Systemic Lupus Erythematosus Susceptibility: An Updated Meta-Analysis and Trial Sequential Analysis

Front Physiol. 2018 Dec 17;9:1793. doi: 10.3389/fphys.2018.01793. eCollection 2018.


Angiotensin-converting enzyme (ACE) gene is indispensable for endothelial control and vascular tone regulatory systems, usually affected in Systemic Lupus Erythematosus (SLE). ACE insertion/deletion (I/D) polymorphism may influence the progress of SLE. Earlier studies have investigated this association without any consistency in results. We performed this meta-analysis to evaluate the precise association between ACE I/D polymorphism and SLE susceptibility. The relevant studies were searched until December, 2017 using Medline (PubMed), Google-Scholar and EMBASE search engines. Twenty-five published studies involving 3,308 cases and 4,235 controls were included in this meta-analysis. Statistically significant increased risk was found for allelic (D vs. I: p = 0.007; OR = 1.202, 95% CI = 1.052-1.374), homozygous (DD vs. II: p = 0.025; OR = 1.347, 95% CI = 1.038-1.748), dominant (DD+ID vs. II: p = 0.002; OR = 1.195, 95% CI = 1.070-1.334), and recessive (DD vs. ID+II: p = 0.023; OR = 1.338, 95% CI = 1.042-1.718) genetic models. Subgroup analysis stratified by Asian ethnicity revealed significant risk of SLE in allelic (D vs. I: p = 0.045; OR = 1.238, 95% CI = 1.005-1.525) and marginal risk in dominant (DD+ID vs. II: p = 0.056; OR = 1.192, 95% CI = 0.995-1.428) models; whereas, no association was observed for Caucasian and African population. Publication bias was absent. In conclusion, ACE I/D polymorphism has significant role in overall SLE risk and it can be exploited as a prognostic marker for early SLE predisposition.

Keywords: ACE gene; SLE; genetic variants; genotypic risk; meta-analysis; polymorphism.