Association of CpG site of MTHFR gene promoter and type 2 diabetes in Moroccan population susceptibility

Abstract

Type 2 diabetes (T2D) is a complex multifactorial metabolic disorder characterized by progressive disease progression, involving varying degrees of insulin resistance and pancreatic islet dysfunction. Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme regulating folate metabolism, and its polymorphisms have been associated with T2D. However, the methylation pattern of the MTHFR gene has not been previously studied. This study aimed to assess the association between T2D and the methylation profile of the MTHFR gene promotor in a Moroccan population. A total of 107 patients with T2D and 100 healthy controls were included in the study. The methylation status of CpG sites in the MTHFR gene promoter was conducted by methylation-specific PCR (MS-PCR). Statistical analyses were performed using SPSS software (version 20). The promoter region of the MTHFR gene was predominantly hyper-methylated in patients with T2D compared to healthy controls (OR: 2.924; 95% CI: 1.285–6.650; p = 0.008). The hypermethylated profile was not influenced by environmental or metabolic factors examined in this study. These findings suggest that hypermethylation of CpG sites in the MTHFR gene promoter is associated with T2D in the Moroccan population, highlighting a potential epigenetic mechanism contributing to the disease.

Keywords: MTHFR Gene, CpG Methylation, MS-PCR, T2D, Morocco