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

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

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Department of Basic Science, College of Dental Sciences, University of Ha'il, Ha'il, Saudi Arabia.
The University College of Medical Sciences and GTB, Guru Teg Bahadur Hospital (University of Delhi), New Delhi, India.
Research and Scientific Studies Unit, College of Nursing & Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
Department of Bioscience & Bioinformatics, Khallikote University, Berhampur, India.
Department of Biotechnology, Institute of Engineering and Technology, Lucknow, India.
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha, Saudi Arabia.


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.


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

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