Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and ischemic Stroke: meta-analysis

• Main Authors: Wei, L. K., Au, A., Menon, S., Griffiths, L. R., Kooi, C. W., Irene, L., Zhao, J., Lee, C., Alekseevna, A. M., Hassan, M. R. A., Aziz, Z. A.
• Format: Article
• Published: W.B. Saunders 2017
• Subjects: TP Chemical technology
• Online Access: http://eprints.utm.my/id/eprint/76552/; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85026329357&doi=10.1016%2fj.jstrokecerebrovasdis.2017.05.048&partnerID=40&md5=91cf035524066ab93cf6786ce8c4f61a

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.