2658-6533Research Results in Biomedicine2658-653310.18413/2658-6533-2020-6-4-0-42179Genetics<strong>An association study of three polymorphisms in the glutathione synthase (<em>GSS</em>) gene with the risk of ischemic stroke</strong><br /> &nbsp;<strong>An association study of three polymorphisms in the glutathione synthase (<em>GSS</em>) gene with the risk of ischemic stroke</strong><br /> &nbsp;BocharovaJulia A.BocharovaJulia A.y_u_l_i_a_03@mail.ru20206400

Background:&nbsp;It is well known that gene polymorphisms of antioxidant defense enzymes contribute to the ischemic stroke (IS) predisposition and affect the severity of its manifestations. The aim of the study: The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of rs13041792, rs1801310 and rs6088660 of the glutathione synthase gene (GSS), involved in the first stage of glutathione biosynthesis, one of the most important low molecular weight antioxidants. Materials and methods: DNA samples from 1288 unrelated individuals of Slavic origin (600 patients with a diagnosis of IS and 688 healthy subjects) were included in the study. Genotyping of GSS gene polymorphisms was done using the MassARRAY-4 system. Functional annotation of SNPs was performed using various online bioinformatic tools. Results: It was found that the G/A rs1801310 genotype was associated with an increased risk of ischemic stroke, regardless of age (OR=1.42 95%CI 1.13-1.77, P=0.002). Association analysis stratified by sex showed that this genotype was associated with an increased risk of IS exclusively in men (OR=1.55 95%CI 1.15-2.10, P=0.004). It was also found that SNP rs6088660 of the GSS gene was associated with the risk of ischemic stroke in women (OR=1.41 95%CI 1.09-2.83, P=0.008). The frequent haplotype rs13041792G-rs1801310G-rs6088660T (OR=1.38 95%CI 1.03-1.83) and the rare haplotype rs13041792A-rs1801310A-rs6088660C (OR=9.78 95%CI 1.15-83.34) were associated with the disease in women. The G/A SNP rs1801310 genotype showed an association with IS risk in men regardless of their smoking status which influenced the disease risk in women, regardless of the rs6088660 genotypes. Conclusion: Bioinformatic analysis showed that transcriptional activity of the GSS gene may depend on the studied polymorphisms due to the fact that they represent the targets for regulation of gene expression by histone modifications and binding transcription factors in a tissue specific manner, including the tissues involved into of ischemic stroke pathophysiology.

Background:&nbsp;It is well known that gene polymorphisms of antioxidant defense enzymes contribute to the ischemic stroke (IS) predisposition and affect the severity of its manifestations. The aim of the study: The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of rs13041792, rs1801310 and rs6088660 of the glutathione synthase gene (GSS), involved in the first stage of glutathione biosynthesis, one of the most important low molecular weight antioxidants. Materials and methods: DNA samples from 1288 unrelated individuals of Slavic origin (600 patients with a diagnosis of IS and 688 healthy subjects) were included in the study. Genotyping of GSS gene polymorphisms was done using the MassARRAY-4 system. Functional annotation of SNPs was performed using various online bioinformatic tools. Results: It was found that the G/A rs1801310 genotype was associated with an increased risk of ischemic stroke, regardless of age (OR=1.42 95%CI 1.13-1.77, P=0.002). Association analysis stratified by sex showed that this genotype was associated with an increased risk of IS exclusively in men (OR=1.55 95%CI 1.15-2.10, P=0.004). It was also found that SNP rs6088660 of the GSS gene was associated with the risk of ischemic stroke in women (OR=1.41 95%CI 1.09-2.83, P=0.008). The frequent haplotype rs13041792G-rs1801310G-rs6088660T (OR=1.38 95%CI 1.03-1.83) and the rare haplotype rs13041792A-rs1801310A-rs6088660C (OR=9.78 95%CI 1.15-83.34) were associated with the disease in women. The G/A SNP rs1801310 genotype showed an association with IS risk in men regardless of their smoking status which influenced the disease risk in women, regardless of the rs6088660 genotypes. Conclusion: Bioinformatic analysis showed that transcriptional activity of the GSS gene may depend on the studied polymorphisms due to the fact that they represent the targets for regulation of gene expression by histone modifications and binding transcription factors in a tissue specific manner, including the tissues involved into of ischemic stroke pathophysiology.

ischemic strokeglutathione metabolismglutathione synthase (GSS)single nucleotide polymorphism (SNP)gene expressiongene-environment interactionssexual dimorphismischemic strokeglutathione metabolismglutathione synthase (GSS)single nucleotide polymorphism (SNP)gene expressiongene-environment interactionssexual dimorphism

The study was supported by the Russian Science Foundation (Agreement No. 15-15-10010).

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