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Front. Physiol. | doi: 10.3389/fphys.2018.01793

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

  • 1Department of Clinical Laboratory Science, College of Applied Medical Sciences, University of Hail, Saudi Arabia
  • 2The University College of Medical Sciences & GTB Hospital, University of Delhi, India
  • 3Research and Scientific Studies Unit, College of Nursing & Allied Health Sciences, Jazan University, Saudi Arabia
  • 4Centre for Life Sciences, Central University of Jharkhand, India
  • 5Department of Biotechnology, Institute of Engineering & Technology, Lucknow, India
  • 6Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al Baha University, 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 3308 cases and 4235 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 to 1.374), homozygous (DD vs II: p=0.025; OR=1.347, 95% CI=1.038 to 1.748), dominant (DD+ID vs II: p=0.002; OR=1.195, 95% CI=1.070 to 1.334), and recessive (DD vs ID+II: p=0.023; OR=1.338, 95% CI=1.042 to 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 to 1.525) and marginal risk in dominant (DD+ID vs II: p=0.056; OR=1.192, 95% CI=0.995 to 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: genetic variants, Ace gene, Polymorphism, Genetic, Meta-analysis, genotypic risk, lupus erythematosus

Received: 27 Mar 2018; Accepted: 28 Nov 2018.

Edited by:

Joseph L. Greenstein, Johns Hopkins University, United States

Reviewed by:

Kumari Sonal Choudhary, University of California, San Diego, United States
Ana Cristina Simões E Silva, Universidade Federal de Minas Gerais, Brazil
Andreas Kronbichler, Innsbruck Medical University, Austria  

Copyright: © 2018 Khan, Dar, Mandal, JAWED, Wahid, Panda, Lohani, Mishra, Akhter and Haque. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Shafiul Haque, Jazan University, Research and Scientific Studies Unit, College of Nursing & Allied Health Sciences, Jizan, Saudi Arabia,