Polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus

Aim. To study the associations of three common single nucleotide variants of the gene encoding antioxidant system enzyme, glutathione reductase GSR with a predisposition to type 2 diabetes (T2D). Materials and methods. The observational mono-center transverse controlled study involved 1032 type 2...

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Autores principales:	Iuliia E. Azarova, Elena Yu. Klyosova, Alexey V. Polonikov
Formato:	article
Lenguaje:	RU
Publicado:	"Consilium Medicum" Publishing house 2021
Materias:	type 2 diabetes mellitus glutathione reductase single nucleotide polymorphism body mass index Medicine R
Acceso en línea:	https://doaj.org/article/f08a8ff005814fcf9fc74622ad19f18d
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spelling	oai:doaj.org-article:f08a8ff005814fcf9fc74622ad19f18d2021-12-01T12:22:36ZPolymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus0040-36602309-534210.26442/00403660.2021.10.201101https://doaj.org/article/f08a8ff005814fcf9fc74622ad19f18d2021-10-01T00:00:00Zhttps://ter-arkhiv.ru/0040-3660/article/viewFile/86883/65083https://doaj.org/toc/0040-3660https://doaj.org/toc/2309-5342Aim. To study the associations of three common single nucleotide variants of the gene encoding antioxidant system enzyme, glutathione reductase GSR with a predisposition to type 2 diabetes (T2D). Materials and methods. The observational mono-center transverse controlled study involved 1032 type 2 diabetics (640 women, 392 men; mean age 61.14.8 years) and 1056 healthy volunteers (676 women, 380 men; mean age 60.96.2 years). Eating habits were evaluated retrospectively according to questionnaire data. A 10 ml blood sample was drawn from all participants in the study for genetic and biochemical tests. Genotyping was done with the use of the iPLEX technology on MassArray System. Results. We first identified the relationship of the polymorphisms rs2551715, rs2911678, rs3757918 of the GSR gene with a reduced risk of developing T2D in the Russian population. At the same time, the protective effects of the variants of the glutathione reductase gene manifested only in individuals with normal body weight provided they consumed fresh vegetables and fruits, whereas in those with insufficient consumption of plant foods, as well as in all overweight and obese patients, the protective effect of GSR was not observed. In patients with T2D, the plasma levels of hydrogen peroxide and the glutathione dimer were sharply increased compared with the controls. We also found that the rs2551715 polymorphism was associated with a lower concentration of hydrogen peroxide in the blood plasma of patients with T2D, while SNP rs2911678 was associated with a decrease in the concentration of the oxidized form of glutathione. Bioinformatical analysis confirmed the positive effect of alternative alleles on GSR expression and revealed the closest protein partners of the enzyme and their joint participation in the metabolism of acetyl-CoA, the catabolism of hydrogen peroxide and the control of cellular redox homeostasis. Conclusion. Polymorphic variants of the GSR gene rs2551715, rs2911678, rs3757918 are associated with a predisposition to T2D, but their relationship with the disease is modulated by the consumption of fresh vegetables and fruits and depends on body mass index.Iuliia E. AzarovaElena Yu. KlyosovaAlexey V. Polonikov"Consilium Medicum" Publishing housearticletype 2 diabetes mellitusglutathione reductasesingle nucleotide polymorphismbody mass indexMedicineRRUТерапевтический архив, Vol 93, Iss 10, Pp 1164-1170 (2021)
institution	DOAJ
collection	DOAJ
language	RU
topic	type 2 diabetes mellitus glutathione reductase single nucleotide polymorphism body mass index Medicine R
spellingShingle	type 2 diabetes mellitus glutathione reductase single nucleotide polymorphism body mass index Medicine R Iuliia E. Azarova Elena Yu. Klyosova Alexey V. Polonikov Polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus
description	Aim. To study the associations of three common single nucleotide variants of the gene encoding antioxidant system enzyme, glutathione reductase GSR with a predisposition to type 2 diabetes (T2D). Materials and methods. The observational mono-center transverse controlled study involved 1032 type 2 diabetics (640 women, 392 men; mean age 61.14.8 years) and 1056 healthy volunteers (676 women, 380 men; mean age 60.96.2 years). Eating habits were evaluated retrospectively according to questionnaire data. A 10 ml blood sample was drawn from all participants in the study for genetic and biochemical tests. Genotyping was done with the use of the iPLEX technology on MassArray System. Results. We first identified the relationship of the polymorphisms rs2551715, rs2911678, rs3757918 of the GSR gene with a reduced risk of developing T2D in the Russian population. At the same time, the protective effects of the variants of the glutathione reductase gene manifested only in individuals with normal body weight provided they consumed fresh vegetables and fruits, whereas in those with insufficient consumption of plant foods, as well as in all overweight and obese patients, the protective effect of GSR was not observed. In patients with T2D, the plasma levels of hydrogen peroxide and the glutathione dimer were sharply increased compared with the controls. We also found that the rs2551715 polymorphism was associated with a lower concentration of hydrogen peroxide in the blood plasma of patients with T2D, while SNP rs2911678 was associated with a decrease in the concentration of the oxidized form of glutathione. Bioinformatical analysis confirmed the positive effect of alternative alleles on GSR expression and revealed the closest protein partners of the enzyme and their joint participation in the metabolism of acetyl-CoA, the catabolism of hydrogen peroxide and the control of cellular redox homeostasis. Conclusion. Polymorphic variants of the GSR gene rs2551715, rs2911678, rs3757918 are associated with a predisposition to T2D, but their relationship with the disease is modulated by the consumption of fresh vegetables and fruits and depends on body mass index.
format	article
author	Iuliia E. Azarova Elena Yu. Klyosova Alexey V. Polonikov
author_facet	Iuliia E. Azarova Elena Yu. Klyosova Alexey V. Polonikov
author_sort	Iuliia E. Azarova
title	Polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus
title_short	Polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus
title_full	Polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus
title_fullStr	Polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus
title_full_unstemmed	Polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus
title_sort	polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus
publisher	"Consilium Medicum" Publishing house
publishDate	2021
url	https://doaj.org/article/f08a8ff005814fcf9fc74622ad19f18d
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_version_	1718405209625985024

Polymorphic variants of glutathione reductase – new genetic markers of predisposition to type 2 diabetes mellitus

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