Role of the SLC30A8 rs13266634 Variant in Predisposition to Type 2 Diabetes Mellitus in Najaf city/Iraq

Abstract

Background: Diabetes mellitus (DM) is known a chronic, multi-systemic of metabolic disorder results in sustained elevations in blood glucose levels, the development of this disease stems from complex etiological factor leading to damage in pancreatic b-cell. The SLC30A8 gene, serves as the genetic template for the zinc transporter member 8 (ZnT8), Validated as a critical susceptibility locus for Type 2 Diabetes Mellitus (T2DM). Objective: To elucidate the genetic association between SLC30A8 single nucleotide polymorphism (SNPs) rs13266634 and the susceptibility to type 2 diabetes mellitus (T2DM) within the Iraqi adult population, to assess the cumulative effect of risk alleles on phenotypic expression of the disease by correlating genetic risk scores with anthropometric indices (e.g. BMI, waist circumference) and parameters of glycemic control (e.g. HbA1C, fasting blood sugar and HOMA-IR). Materials and Methods: A case-control study involved 151 patients with type 2 diabetes mellitus from the Diabetic Center at Al-Sader Teaching Hospital and Al-Hakeem general hospital in Najaf City, Iraq, who were compared to 146 healthy control group. Both groups satisfied the inclusion requirements. blood taken from all participants and standard methodologies were employed to assess fasting blood glucose (FBS), serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and insulin levels and serum Zinc. A HOMO-IR calculation was conducted. The SLC30A8 gene rs13266634 SNP was genotyped using the Polymerase Chain Reaction-Allele Specific (PCR-AS) approach. Results: Rs13266634 was identified to be an additional susceptibility variant for T2DM in the Iraqi population. The association between rs13266634 and T2DM was found to be independent of the other polymorphisms investigated, with the majority of the association being attributed to impaired glycemic control and not lipid metabolism. The association is supported by prior investigations demonstrating the structural and functional impacts of rs13266634 on ZnT8 and insulin secretion kinetics. Conclusion: Single nucleotide polymorphism of the SLC30A8 gene (rs13266634) independently increased T2DM risk, primarily through mechanisms related to impaired β-cell function and glycemic regulation rather than lipid metabolism.