TY - JOUR
T1 - Identification of glyoxalase 1 polymorphisms associated with enzyme activity
AU - Peculis, Raitis
AU - Konrade, Ilze
AU - Skapare, Elina
AU - Fridmanis, Davids
AU - Nikitina-Zake, Liene
AU - Lejnieks, Aivars
AU - Pirags, Valdis
AU - Dambrova, Maija
AU - Klovins, Janis
N1 - Funding Information:
This study was supported by the Latvian Council of Science (grant 10.0010.04 ), Latvian State Research Program in Biomedicine 4.2 , and the European Foundation for the Study of Diabetes (EFSD) grant program of the New Horizons Collaborative Research Initiative . We acknowledge the Genome Database of Latvian Population, Latvian Biomedical Research and Study Center for providing data and DNA samples. Raitis Peculis was supported by ESF grant 1DP/1.1.1.2.0/09/APIA/VIAA/150 . Publication expenses were covered by ERAF grant 2DP/2.1.1.2.0/10/APIA/VIAA/004.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013/2/15
Y1 - 2013/2/15
N2 - The glyoxalase system and its main enzyme, glyoxalase 1 (GLO1), protect cells from advanced glycation end products (AGEs), such as methylglyoxal (MG) and other reactive dicarbonyls, the formation of which is increased in diabetes patients as a result of excessive glycolysis. MG is partly responsible for harmful protein alterations in living cells, notably in neurons, leading to their dysfunction, and recent studies have shown a negative correlation between GLO1 expression and tissue damage. Neuronal dysfunction is a common diabetes complication due to elevated blood sugar levels, leading to high levels of AGEs. The aim of our study was to determine whether single nucleotide polymorphisms (SNPs) in the GLO1 gene influence activity of the enzyme. In total, 125 healthy controls, 101 type 1 diabetes, and 100 type 2 diabetes patients were genotyped for three common SNPs, rs2736654 (A111E), rs1130534 (G124G), and rs1049346 (5'-UTR), in GLO1. GLO1 activity was determined in whole blood lysates for all participants of the study. Our results showed a significant association between the minor alleles rs1130534 and rs1049346 and decreased enzyme activity (P=0.001 and P=2.61×10-5, respectively). Increased allelic counts of the risk alleles were strongly associated with decreased GLO1 activity (standardised β=-0.24, P=2.15×10-5), indicating independent actions of these variants on GLO1 activity, as supported by the haplotype analysis. We showed for the first time an association between genetic variants with GLO1 enzyme activity in humans. SNPs in GLO1 can be used to predict enzyme activity and detoxifying capabilities, but further studies are needed to link these SNPs with common complications in diabetes.
AB - The glyoxalase system and its main enzyme, glyoxalase 1 (GLO1), protect cells from advanced glycation end products (AGEs), such as methylglyoxal (MG) and other reactive dicarbonyls, the formation of which is increased in diabetes patients as a result of excessive glycolysis. MG is partly responsible for harmful protein alterations in living cells, notably in neurons, leading to their dysfunction, and recent studies have shown a negative correlation between GLO1 expression and tissue damage. Neuronal dysfunction is a common diabetes complication due to elevated blood sugar levels, leading to high levels of AGEs. The aim of our study was to determine whether single nucleotide polymorphisms (SNPs) in the GLO1 gene influence activity of the enzyme. In total, 125 healthy controls, 101 type 1 diabetes, and 100 type 2 diabetes patients were genotyped for three common SNPs, rs2736654 (A111E), rs1130534 (G124G), and rs1049346 (5'-UTR), in GLO1. GLO1 activity was determined in whole blood lysates for all participants of the study. Our results showed a significant association between the minor alleles rs1130534 and rs1049346 and decreased enzyme activity (P=0.001 and P=2.61×10-5, respectively). Increased allelic counts of the risk alleles were strongly associated with decreased GLO1 activity (standardised β=-0.24, P=2.15×10-5), indicating independent actions of these variants on GLO1 activity, as supported by the haplotype analysis. We showed for the first time an association between genetic variants with GLO1 enzyme activity in humans. SNPs in GLO1 can be used to predict enzyme activity and detoxifying capabilities, but further studies are needed to link these SNPs with common complications in diabetes.
KW - Diabetes
KW - Glyoxalase 1
KW - SNP
UR - http://www.scopus.com/inward/record.url?scp=84872276698&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2012.11.009
DO - 10.1016/j.gene.2012.11.009
M3 - Article
C2 - 23201419
AN - SCOPUS:84872276698
SN - 0378-1119
VL - 515
SP - 140
EP - 143
JO - Gene
JF - Gene
IS - 1
ER -