Loo Keat Wei1, Anthony Au2, Saras Menon3, Lyn R Griffiths3, Cheah Wee Kooi4, Looi Irene5, Jiangyang Zhao6, Chaeyoung Lee7, Avdonina Maria Alekseevna8, Muhammad Radzi Abdul Hassan9, Zariah Abdul Aziz10. 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.
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. Crown
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. Crown
Authors: Christoph J Griessenauer; Sean Farrell; Atom Sarkar; Ramin Zand; Vida Abedi; Neil Holland; Andrew Michael; Christopher L Cummings; Raghu Metpally; David J Carey; Oded Goren; Neil Martin; Philipp Hendrix; Clemens M Schirmer Journal: J Cereb Blood Flow Metab Date: 2018-09-05 Impact factor: 6.200