Ассоциация полиморфных вариантов гена каталитической субъединицы глутаматцистеинлигазы с клиническими характеристиками ишемического инсульта

YA Bocharova

doi:10.24075/brsmu.2021.007

Abstract

An imbalance between the production of reactive oxygen species and their neutralization lies at the core of oxidative stress implicated in ischemic stroke (IS) and the subsequent brain tissue damage. The aim of this study was to investigate the effects of common polymorphic variants of the glutamate cysteine ligase catalytic subunit gene on the extent of brain damage and clinical manifestations in patients with ischemic stroke. A total of 589 ischemic stroke survivors were genotyped for 6 single nucleotide polymorphisms (SNPs) of the GCLC gene, including rs12524494, rs17883901, rs606548, rs636933, rs648595 and rs761142, using a MassARRAY-4 analyzer. The study found that genotypes rs636933-G/A-A/A (р = 0.009) and rs761142-A/C-C/C (р = 0.015) were associated with an enlargement of the cerebral lesion size. Genotypes rs12524494-G/G (р = 0.05) and rs606548-T/T (р = 0.003) were associated with a risk of 2 or more IS episodes. Genotype rs17883901-G/A was associated with early onset of IS (р = 0.004). The study revealed multiple associations of GCLC SNPs with the clinical manifestations of ischemic stroke. Thus, GCLC polymorphisms are important DNA markers affecting the size of the cerebral lesion in patients with ischemic stroke and are associated with age at onset, the number of past strokes and the clinical manifestations of the disease.

Highlights

An imbalance between the production of reactive oxygen species and their neutralization lies at the core of oxidative stress implicated in ischemic stroke (IS) and the subsequent brain tissue damage
We found that polymorphisms rs636933 and rs761142 were significantly associated with the size of the cerebral lesion in patients with ischemic stroke regardless of their age or sex
Our pilot study looked into the effects produced by the polymorphic variants of the gene encoding the key enzyme of glutathione synthesis on the extent of cerebral damage and the clinical manifestations of IS

Summary

Introduction

An imbalance between the production of reactive oxygen species and their neutralization lies at the core of oxidative stress implicated in ischemic stroke (IS) and the subsequent brain tissue damage. The aim of this study was to investigate the effects of common polymorphic variants of the glutamate cysteine ligase catalytic subunit gene on the extent of brain damage and clinical manifestations in patients with ischemic stroke. Полиморфные варианты гена GCLC являются значимыми ДНК-маркерами, влияющими на зону инфаркта мозга у больных ишемическим инсультом, ассоциированы с возрастом дебюта первого инсульта, числом перенесенных инсультов и клиническими проявлениями болезни. Multiple studies have demonstrated that redox homeostasis disturbances manifesting as an imbalance between the production of reactive oxygen species and their neutralization lie at the core of oxidative stress implicated in IS and the subsequent brain tissue damage [3].

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