Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis

Wei LK 1 , Au A 2 , Menon S 3 , Griffiths LR 3 , Kooi CW 4 , Irene L 5 Show all authors , Zhao J 6 , Lee C 7 , Alekseevna AM 8 , Hassan MRA 9 , Aziz ZA 10

Affiliations 

  • 1 Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, Bandar Barat, Kampar, Perak, Malaysia. Electronic address: wynnelkw@gmail.com
  • 2 Department of Bioprocess Engineering, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, Skudai, Malaysia
  • 3 Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, Queensland, Australia
  • 4 Department of Medicine and Clinical Research Centre, Taiping Hospital, Jalan Tamingsari, Taiping, Perak, Malaysia
  • 5 Department of Medicine and Clinical Research Centre, Hospital Seberang Jaya, Jalan Tun Hussein Onn, Seberang Jaya, Pulau Pinang, Malaysia
  • 6 Department of Clinical Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
  • 7 School of Systems Biomedical Science, Soongsil University, 511 Sangdo-dong, Dongjak-gu, Seoul, Republic of Korea
  • 8 Laboratory of Biological Microchips, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
  • 9 Medical Department, Hospital Sultanah Bahiyah, Alor Star, Kedah, Malaysia
  • 10 Neurology Division, Department of Medicine, Hospital Sultanah Nur Zahirah, Jalan Sultan Mahmud, Kuala Terengganu, Kuala Terengganu, Malaysia
J Stroke Cerebrovasc Dis, 2017 Nov;26(11):2482-2493.
PMID: 28760411 DOI: 10.1016/j.jstrokecerebrovasdis.2017.05.048

Abstract

INTRODUCTION: The association between ischemic stroke and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and apolipoprotein E (ApoE) ε2ε3ε4 remains inconclusive. Therefore, this updated meta-analysis aimed to clarify the presumed influence of genetic polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of all individual association studies.

METHODS: All case-control studies published in different languages such as English, Japanese, Korean, Spanish, Chinese, Hungarian, Ukrainian, or Russian were identified from databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via fixed- and random-effect models. Sensitivity analysis, heterogeneity test, Hardy Weinberg Equilibrium, and Egger's regression analyses were performed in this study.

RESULTS: A total of 490 case-control studies with 138,592 cases and 159,314 controls were included in this meta-analysis. Pooled ORs from all the genetic models indicated that MTHFR 677TT and 1298CC, eNOS +894TT and VNTR, PDE4D SNP 83, ACE DD, AGT 235TT, PON1 192RR, and ApoE ε4 polymorphisms were increasing the risks of ischemic stroke. Nevertheless, PDE4D SNP 87 and eNOS -786T>C polymorphisms are not associated with ischemic stroke risks.

CONCLUSIONS: Hence, the evidence from this meta-analysis concluded that MTHFR (677C>T and 1298A>C), eNOS (+894G>T and VNTR), PDE4D SNP 83, ACE I/D, AGT 235M>T, PON1 192Q>R, and ApoE ε2ε3ε4 polymorphisms predispose individuals to ischemic stroke.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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