Identification of glyoxalase 1 polymorphisms associated with enzyme activity |
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| Authors: | Raitis Peculis Ilze Konrade Elina Skapare Davids Fridmanis Liene Nikitina-Zake Aivars Lejnieks Valdis Pirags Maija Dambrova Janis Klovins |
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| Affiliation: | 1. Latvian Biomedical Research and Study Centre, Ratsupites str 1, Riga, LV-1067, Latvia;2. Riga East Clinical University Hospital, Hipokrata str 2, Riga, LV–1038, Latvia;3. Latvian Institute of Organic Synthesis, Aizkraukles str 21, Riga, LV-1006, Latvia;4. Riga Stradins University, Dzirciema str 16, Riga, LV-1007, Latvia;5. Faculty of Medicine, University of Latvia, Sarlotes str. 1a, Riga, LV-1001, Latvia;6. Department of Endocrinology, Pauls Stradins Clinical University Hospital, Pilsonu str 13, Riga, LV-1002, Latvia |
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| Abstract: | 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. |
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| Keywords: | 5&prime -UTR, 5 prime untranslated region ACE inhibitor/ARB, angiotensin converting enzyme inhibitors and angiotensin receptor blocker AGE, advanced glycation end product BMI, body mass index EMP2, corrected empirical p-value GABA, gamma-aminobutyric acid GLO1, glyoxalase 1 GLO2, glyoxalase 2 Hap, haplotype HbA1c, glycated hemoglobin HDL, high-density lipoprotein hs-CRP, high-sensitivity C-reactive protein LD, linkage disequilibrium LDL, low-density lipoprotein MAF, minor allele frequencies MALDI-TOF, matrix-assisted laser desorption/ionization time-of-flight mass spectrometer MG, methylglyoxal SD, standard deviation SNP, single nucleotide polymorphism T1D, type 1 diabetes T2D, type 2 diabetes U/g Hb, units per gram hemoglobin |
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