Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes
- PDF / 989,724 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 91 Downloads / 160 Views
ORIGINAL ARTICLE
Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes Iuliia Azarova1,2 · Elena Klyosova2 · Victor Lazarenko3 · Alexander Konoplya1 · Alexey Polonikov4,5 Received: 19 March 2020 / Accepted: 8 July 2020 © Springer Nature B.V. 2020
Abstract Oxidative stress contributes to the pathogenesis of type 2 diabetes (T2D). This study investigated whether single nucleotide polymorphisms (SNPs) at genes encoding glutamate cysteine ligase catalytic (rs12524494, rs17883901, rs606548, rs636933, rs648595, rs761142 at GCLC) and modifier (rs2301022, rs3827715, rs7517826, rs41303970 at GCLM) subunits are associated with susceptibility to type 2 diabetes. 2096 unrelated Russian subjects were enrolled for the study. Genotyping was done with the use of the MassArray System. Plasma levels of reactive oxygen species (ROS) and glutathione in the study subjects were analyzed by fluorometric and colorimetric assays, respectively.The present study found, for the first time, an association of SNP rs41303970 in the GCLM gene with a decreased risk of T2D (P = 0.034, Q = 0.17). Minor alleles such as rs12524494-G GCLC gene (P = 0.026, Q = 0.17) and rs3827715-C GCLM gene (P = 0.03, Q = 0.17) were also associated with reduced risk for T2D. Protective effects of variant alleles such as rs12524494-G at GCLC (P = 0.02, Q = 0.26) and rs41303970-A GCLM (P = 0.013, Q = 0.25) against the risk of T2D were seen solely in nonsmokers. As compared with healthy controls, diabetic patients had markedly increased levels of ROS and decreased levels of total GSH in plasma. Interestingly, fasting blood glucose level positively correlated with oxidized glutathione concentration (rs = 0.208, P = 0.01). Three SNPs rs17883901, rs636933, rs648595 at GCLC and one rs2301022 at GCLM were associated with decreased levels of ROS, while SNPs rs7517826, rs41303970 at GCLM were associated with increased levels of total GSH in plasma. Single nucleotide polymorphisms in genes encoding glutamate cysteine ligase subunits confer protection against type 2 diabetes and their effects are mediated through increased levels of glutathione. Keywords Type 2 diabetes mellitus · Oxidative stress · Reactive oxygen species · Glutathione · Glutamate cysteine ligase · Single nucleotide polymorphism Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05647-5) contains supplementary material, which is available to authorized users. * Iuliia Azarova [email protected]; [email protected] Elena Klyosova [email protected] Victor Lazarenko [email protected] Alexander Konoplya [email protected]
Alexey Polonikov [email protected]; [email protected]
1
Department of Biological Chemistry, Kursk State Medical University, 3 Karl Marx Street, Kursk, Russian Federation 305041
Laboratory of Biochemical Genetics and Metabolomics, Research Institute for Genetic and Molecular Epidemiology,
2
Kursk State Medical University, 18 Yamskaya St., Kursk, Russian F
Data Loading...
