PMID- 31738890 OWN - NLM STAT- MEDLINE DCOM- 20200413 LR - 20200413 IS - 1096-0384 (Electronic) IS - 0003-9861 (Linking) VI - 679 DP - 2020 Jan 15 TI - Micro RNA 146a gene variant / TNF-alpha / IL-6 / IL-1 beta; A cross-link axis inbetween oxidative stress, endothelial dysfunction and neuro-inflammation in acute ischemic stroke and chronic schizophrenic patients. PG - 108193 LID - S0003-9861(19)30761-1 [pii] LID - 10.1016/j.abb.2019.108193 [doi] AB - This work was purposed to speculate the possible association of rs2910164hsa-miR-146a C>G gene single nucleotide polymorphism in the pathogenesis of schizophrenia and subsequently their relevance to neuro-inflammatory, vascular and oxidative stress pathways as acute ischemic stroke (AIS) risk factors in chronic schizophrenic patients. 450 subjects, 150 healthy controls (group I), 150 chronic schizophrenic patients without any evidences of stroke (group II) and 150 chronic schizophrenic patients with AIS (group III) were included. Genotypes (CC, CG&GG) for hsa-mir-146a gene polymorphism were identified using polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP technique. Tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 1beta (IL-1 beta), plasminogen activator-inhibitor 1 (PAI-1), thrombomodulin (TM) and 8-Hydroxy-2-deoxyguanosine (8-OHdG) serum levels were immunoassayed. Complete lipid profile was estimated. The CG and GG hsa-miR-146a genotypes were associated with increased risk of both schizophrenia and AIS in schizophrenic patients with thrombomodulin levels decrement in group II& III. On the other side, the risk genotypes were associated significantly with positive and negative syndrome scale PANSS scores, TNF-alpha, IL-6, IL-1 beta, PAI-1, and 8-OHdG increment levels in both groups II & III. By contrast, the CG and GG hsa-miR-146a genotypes did not affect the neuro-inflammatory and oxidative stress markers in healthy controls. These findings illustrate a new mechanism strengthening the occurrence of oxidative stress and DNA damage as a result of the neuro-inflammatory and endothelial dysfunction status originated from the hsa-miR-146a C>G gene single nucleotide polymorphism, thus, confirming their role in the pathogenesis of schizophrenia and its AIS risk. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Ibrahim, Rowida Raafat AU - Ibrahim RR AD - Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Tanta University, Egypt. Electronic address: rowaida.yousef@med.tanta.edu.eg. FAU - Amer, Reham A AU - Amer RA AD - Neuro-psychiatry Department, Faculty of Medicine, Tanta University, Egypt. FAU - Abozeid, Abeer A AU - Abozeid AA AD - Physiology Department, Faculty of Medicine, Tanta University, Egypt. FAU - Elsharaby, Radwa Mahmoud AU - Elsharaby RM AD - Clinical Pathology Department, Faculty of Medicine, Tanta University, Egypt. FAU - Shafik, Noha M AU - Shafik NM AD - Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Tanta University, Egypt. LA - eng PT - Journal Article DEP - 20191115 PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 0 (IL1B protein, human) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (MIRN146 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Acute Disease MH - Brain Ischemia/*complications MH - Chronic Disease MH - DNA Damage/genetics MH - Endothelial Cells/*pathology MH - Genetic Predisposition to Disease/genetics MH - Humans MH - Inflammation/genetics/metabolism/pathology MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Male MH - MicroRNAs/*genetics MH - Middle Aged MH - Oxidative Stress/*genetics MH - *Polymorphism, Single Nucleotide MH - Schizophrenia/*genetics/metabolism/pathology MH - Signal Transduction/genetics MH - Stroke/complications/*genetics/metabolism/pathology MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Acute ischemic stroke OT - DNA damage OT - Polymorphism OT - Schizophrenia OT - microRNA-146a EDAT- 2019/11/19 06:00 MHDA- 2020/04/14 06:00 CRDT- 2019/11/19 06:00 PHST- 2019/08/30 00:00 [received] PHST- 2019/11/09 00:00 [revised] PHST- 2019/11/12 00:00 [accepted] PHST- 2019/11/19 06:00 [pubmed] PHST- 2020/04/14 06:00 [medline] PHST- 2019/11/19 06:00 [entrez] AID - S0003-9861(19)30761-1 [pii] AID - 10.1016/j.abb.2019.108193 [doi] PST - ppublish SO - Arch Biochem Biophys. 2020 Jan 15;679:108193. doi: 10.1016/j.abb.2019.108193. Epub 2019 Nov 15.