ABSTRACT
Type 2 diabetes mellitus (T2DM) is a common polygenic disease with associated comorbidities. Obesity is a major risk factor for the development of T2DM. The aim of this study is to determine the allele and genotype frequency of peroxisome proliferator-activated receptor-γ (PPARγ) rs1801282, fat mass and obesity-associated protein (FTO) rs9939609, and melanocortin 4 receptor (MC4R) rs2229616 polymorphisms and their association with risk of T2DM in the western Saudi population as mediators of adiposity phenotypes. In a cross-sectional prospective study, genomic DNA from control and T2DM patients were isolated and genotyped for these single-nucleotide polymorphisms. There was a significant association of the MC4R rs2229616 variant with T2DM, but no association with T2DM was detected with PPARγ rs1801282 or FTO rs9939609. The combination of C/C for PPARγ rs1801282, A/A for FTO rs9939609, and C/C for MC4R rs2229616 increased the risk of T2DM by 1.82. The A/T genotype for FTO rs9939609 was predicted to decrease the risk of T2DM when combined with C/C for PPARγ rs1801282 and C/C for MC4R rs2229616 or C/C for PPARγ rs1801282 and C/T MC4R rs2229616. In conclusion, our study showed the risk of the assessed variants for the development of T2DM in the Saudi population.
Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Diabetes Mellitus, Type 2/genetics , PPAR gamma/genetics , Receptor, Melanocortin, Type 4/genetics , Adiposity , Adult , Alleles , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Body Mass Index , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 2/metabolism , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genetic Variation/genetics , Genotype , Humans , Male , Middle Aged , Obesity/genetics , PPAR gamma/metabolism , Phenotype , Polymorphism, Single Nucleotide/genetics , Prospective Studies , Receptor, Melanocortin, Type 4/metabolism , Risk Factors , Saudi Arabia/epidemiologyABSTRACT
INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major global health problem that is progressively affected by genetic and environmental factors. The aim of this study is to determine the influence of solute carrier family 22 member 1 (SLC22A1) rs628031 and rs461473, and ataxia telangiectasia mutated (ATM) rs11212617 polymorphisms on the risk of T2DM in Saudi Arabia by considering many parameters associated with glycemic control of T2DM, such as body mass index (BMI), fasting blood glucose, glycated hemoglobin (HbA1c), and triglyceride. METHODS: In a case-control study, genomic DNA from controls and diabetic groups was isolated and genotyped for each single-nucleotide polymorphism. RESULTS: There were significant correlations between T2DM and both BMI and HbA1c. Significant associations between G/G and A/G genotypes of rs628031 and rs461473 variants of SLC22A1 and high levels of HbA1c were detected. Therefore, G was predicted to be the risk allele among the assessed SLC22A1 variants. A significant correlation was observed between A/A and A/C genotypes of the rs11212617 polymorphism of ATM and elevated HbA1c. Relative risk calculation confirmed A to be the risk allele in the T2DM population. CONCLUSION: Our study showed the risk of the assessed SLC22A1 and ATM variants on glycemic control parameters in diabetic patients.