Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes
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, r...
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Published in | Molecular biology reports Vol. 47; no. 8; pp. 5793 - 5805 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Dordrecht
Springer Netherlands
01.08.2020
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
ISSN | 0301-4851 1573-4978 1573-4978 |
DOI | 10.1007/s11033-020-05647-5 |
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Summary: | 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 (r
s
= 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
ISSN: | 0301-4851 1573-4978 1573-4978 |
DOI: | 10.1007/s11033-020-05647-5 |