The genetic polymorphisms and activity of glyoxalase 1 as a risk factor for acute coronary syndrome in South Indians with type 2 diabetes mellitus

Sushmita Bora; Prashant Shankarrao Adole; Kolar Vishwanath Vinod; Ajith Ananthakrishna Pillai; Shaheer Ahmed

doi:10.1016/j.gene.2023.147701

The genetic polymorphisms and activity of glyoxalase 1 as a risk factor for acute coronary syndrome in South Indians with type 2 diabetes mellitus

Gene. 2023 Nov 15:885:147701. doi: 10.1016/j.gene.2023.147701. Epub 2023 Aug 10.

Authors

Sushmita Bora¹, Prashant Shankarrao Adole², Kolar Vishwanath Vinod³, Ajith Ananthakrishna Pillai⁴, Shaheer Ahmed⁴

Affiliations

¹ Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India.
² Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India. Electronic address: prashant.adole@gmail.com.
³ Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India.
⁴ Department of Cardiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India.

PMID: 37572800
DOI: 10.1016/j.gene.2023.147701

Abstract

Objective: The individuals' genetic traits predispose them to a higher or lower risk of Type 2 diabetes mellitus (T2DM) and its complications, for example, acute coronary syndrome (ACS). As carbonyl stress is responsible for the pathogenesis and complications of T2DM, and glyoxalase 1 (GLO1) is the most crucial determinant of carbonyl stress, the study aimed to explore the association between GLO1 gene polymorphism, GLO1 activity in red blood cell (RBC), plasma methylglyoxal (MG) levels, and ACS risk in South Indian T2DM patients.

Methods: A total of 150 T2DM patients with ACS as cases and 150 T2DM patients without ACS as controls were recruited in a case-control study. The rs4746, rs1049346 and rs1130534 of the GLO1 gene were analysed using TaqMan allele discrimination assay. The RBC GLO1 activity and plasma MG levels were measured.

Results: Significantly lower RBC GLO1 activity and higher plasma MG levels were found in cases compared to controls (p < 0.001 and p = 0.008, respectively). The genotype and allele frequencies of rs1049346 significantly differed between cases and controls (p < 0.001). For rs1130534 and rs1049346, no significant difference was found. For rs1049346, the TT and CC genotypes were associated with higher (p = 0.002) and lower (p = 0.001) ACS risk, respectively, in various genetic models. The TT genotype of rs1049346 was associated with lower RBC GLO1 activity (p = 0.004) and higher MG level (p = 0.010). In haplotype analysis, higher ACS susceptibility with the TAT haplotype (p < 0.001) and lower ACS susceptibility with the TAC haplotype (p < 0.001) were observed. Also, lower RBC GLO1 activity was associated with the TAT haplotype (p = 0.002).

Conclusions: The rs1049346 of the GLO1 gene may be associated with ACS risk in South Indian T2DM patients, and the T and C allele might be essential precipitating and protective factors, respectively.

Keywords: Acute coronary syndrome; Carbonyl stress; Glyoxalase 1; Single nucleotide polymorphism; Type 2 diabetes mellitus.

MeSH terms

Acute Coronary Syndrome* / genetics
Case-Control Studies
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / genetics
Genetic Predisposition to Disease
Genotype
Humans
Lactoylglutathione Lyase* / genetics
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Pyruvaldehyde
Risk Factors

Substances

Lactoylglutathione Lyase
Pyruvaldehyde