Clinical Implications of Glyoxalase1 Gene Polymorphism and Elevated Levels of the Reactive Metabolite Methylglyoxal in the Susceptibility of Type 2 Diabetes Mellitus in the Patients from Asir and Tabuk Regions of Saudi Arabia

Muhanad Alhujaily; Mohammad Muzaffar Mir; Rashid Mir; Mushabab Ayed Abdullah Alghamdi; Javed Iqbal Wani; Zia Ul Sabah; Imadeldin Elfaki; Tarig Mohammad Saad Alnour; Mohammed Jeelani; Mosleh Mohammad Abomughaid; Samir Abdulkarim Alharbi

doi:10.3390/jpm12040639

Clinical Implications of Glyoxalase1 Gene Polymorphism and Elevated Levels of the Reactive Metabolite Methylglyoxal in the Susceptibility of Type 2 Diabetes Mellitus in the Patients from Asir and Tabuk Regions of Saudi Arabia

J Pers Med. 2022 Apr 15;12(4):639. doi: 10.3390/jpm12040639.

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia.
² Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
³ Prince Fahd Bin Sultan Research Chair, Department of MLT, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.
⁴ Department of Internal Medicine, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
⁵ Department of Internal Medicine, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia.
⁶ Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
⁷ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia.

Abstract

Diabetes mellitus constitutes a big challenge to the global health care system due to its socioeconomic impacts and very serious complications. The incidence and the prevalence rate are increased in the Gulf region including the KSA. Type 2 diabetes mellitus (T2DM) is caused by diverse risk factors including obesity, unhealthy dietary habits, physical inactivity, smoking and genetic factors. The molecular genetic studies have helped in the detection of many single nucleotide polymorphisms (SNP) with different diseases including cancers, cardiovascular diseases and T2DM. The glyoxalase 1 (GLO1) is a detoxifying enzyme and catalyzes the elimination of the cytotoxic product methylglyoxal (MG) by converting it to D-lactate, which is not toxic to tissues. MG accumulation is associated with the pathogenesis of different diseases including T2DM. In this study, we have investigated the association of the glyoxalase 1 SNPs (rs2736654) rs4746 C>A and rs1130534 T>A with T2DM using the amplification refractory mutation system PCR. We also measured the concentration of MG by ELISA in T2DM patients and matched heathy controls. Results show that the CA genotype of the GLO rs4647 A>C was associated with T2DM with OR = 2.57, p-value 0.0008 and the C allele was also associated with increased risk to T2DM with OR = 2.24, p-value = 0.0001. It was also observed that AT genotype of the rs1130534 was associated with decreased susceptibility to T2DM with OR = 0.3, p-value = 0.02. The A allele of rs1130534 was also associated with reduced risk to T2DM with PR = 0.27 = 0.006. In addition, our ELISA results demonstrate significantly increased MG concentrations in serum of the T2DM patients. We conclude that the GLO1 SNP may be associated with decreased enzyme activity and a resultant susceptibility to T2DM. Further well-designed studies in different and large patient populations are recommended to verify these findings.

Keywords: GLO1-glyoxalase-1; T2DM; methylglyoxal; rs1130534 T>A; rs2736654 C>A; single nucleotide polymorphism; type 2 diabetes in Saudi Arabia.

Grants and funding

49/1442/"Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia