Determination of Glyoxalase-1 levels and Identification of Genetic Variants in GLO1 Gene in Patients of Diabetic Nephropathy

Pak J Med Sci. 2024 Mar-Apr;40(4):652-656. doi: 10.12669/pjms.40.4.8258.

Abstract

Objective: To determine the association of diabetic nephropathy with glyoxalase-1 enzyme levels and a genetic missense variation (SNP rs4746) in its gene (GLO-1).

Methods: This cross-sectional comparative study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi from November 2020 to December 2022. One hundred patients and one hundred and thirteen healthy controls were enrolled using the nonprobability convenience sampling method. Medical history and 10ml blood were obtained from each individual after written informed consent. Blood samples were subjected to biochemical tests and DNA extraction which was later used for single nucleotide polymorphism (SNP) analysis (C332C variant of rs4741 GLO-1 gene) using Tetra primer ARMS PCR and gel electrophoresis. Glyoxalase-1 enzyme activity in serum was measured using ELISA.

Results: There was a significant difference in serum glyoxalase-1 levels in the two groups (p-value< 0.001). The patient group had lower levels (16.24 ± 22.51mg/dl) of glyoxalase-1 as compared to the control group (48.70 ± 42.54mg/dl). In genotypic analysis, 98 out of 100 control individuals had AA genotype-while only one had CC and another AC genotype. In the patient group, 94 out of 100 patients showed AA genotype, three AC, and three CC genotypes. As the statistical significance (p-value) was 0.37, there was no significant association found between AC or CC genotype and diabetic nephropathy.

Conclusion: Glyoxalase-1 levels are linked to the development of diabetic nephropathy in our patients while a known missense variant rs4746 in the GLO-1 gene is not associated with increased risk.

Keywords: Advanced Glycation End products (AGEs); Diabetic Nephropathy; Glyoxalase-1 (GLO1); Methylglyoxal; SNP rs4746.