AUTHOR=Khan Saif , Dar Sajad A. , Mandal Raju K. , Jawed Arshad , Wahid Mohd , Panda Aditya K. , Lohani Mohtashim , Mishra B. N. , Akhter Naseem , Haque Shafiul 

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

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01793

DOI=10.3389/fphys.2018.01793

ISSN=1664-042X

ABSTRACT=<p>Angiotensin-converting enzyme (<italic>ACE</italic>) gene is indispensable for endothelial control and vascular tone regulatory systems, usually affected in Systemic Lupus Erythematosus (SLE). <italic>ACE</italic> 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 <italic>ACE</italic> 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: <italic>p</italic> = 0.007; <italic>OR</italic> = 1.202, 95% <italic>CI</italic> = 1.052–1.374), homozygous (DD vs. II: <italic>p</italic> = 0.025; <italic>OR</italic> = 1.347, 95% <italic>CI</italic> = 1.038–1.748), dominant (DD+ID vs. II: <italic>p</italic> = 0.002; <italic>OR</italic> = 1.195, 95% <italic>CI</italic> = 1.070–1.334), and recessive (DD vs. ID+II: <italic>p</italic> = 0.023; <italic>OR</italic> = 1.338, 95% <italic>CI</italic> = 1.042–1.718) genetic models. Subgroup analysis stratified by Asian ethnicity revealed significant risk of SLE in allelic (D vs. I: <italic>p</italic> = 0.045; <italic>OR</italic> = 1.238, 95% <italic>CI</italic> = 1.005–1.525) and marginal risk in dominant (DD+ID vs. II: <italic>p</italic> = 0.056; <italic>OR</italic> = 1.192, 95% <italic>CI</italic> = 0.995–1.428) models; whereas, no association was observed for Caucasian and African population. Publication bias was absent. In conclusion, <italic>ACE</italic> I/D polymorphism has significant role in overall SLE risk and it can be exploited as a prognostic marker for early SLE predisposition.</p>