MTHFR Polymorphism in Congo Type 2 Diabetics: Prevalence of c.677CT and c.1298AC Mutations and Degenerative Complications

Abstract

Introduction: Type 2 diabetes (T2DM) is a multifactorial disease with serious complications, particularly degenerative. Currently, several genes have been identified in its pathogenesis, including the 5,10-methylene tetrahydrofolate reductase (MTHFR) gene with an association of the c.677C>T and c.1298A>C variants. The aim of this study was first to investigate the frequency of these variants in Congolese subjects with T2DM and to compare them with healthy controls. Secondly, to establish a correlation between these genotypes and the degenerative complications observed in T2DM patients. Material and methods:This was a prospective casecontrol study conducted over a two-year period. It involved 100 individuals with T2DM and 50 healthy, non-diabetic controls. The study method was based on DNA sequencing using the Sanger method, looking for the c.677CT and c.1298AC variants in the MTHFR gene. Results:In the DT2 group, the study identified heterozygous genotypes MTHFR1298AC in 18% of T2DM cases and MTHFR 677CT in 17% of cases. The homozygous MTHFR 1298CC genotype was detected in 2% of individuals. It should be noted that combinations of these two mutations were identified in some T2DM subjects, namely: (677CT; 1298AC) in 1% of cases and (677CC; 1298CC) in 2% of cases.In the control group, heterozygous genotypes MTHF R1298AC and MTHFR 677CT were identified in 6% and 4% of cases respectively. The difference was statistically significant (p = 0.024; p = 0.048).Degenerative complications (stroke, neuropathy, ischaemic heart disease) were observed in 58.8% (20/34) of T2DM carrying the mutation exclusively in the heterozygous MTHFR 677CT form and in 44.1% (15/34) of T2DM carrying the mutation exclusively in the heterozygous MTHFR 1298AC form. Conclusion:The c.677C>T and c.1298A>C variations of the MTHFR gene, identified in Congolese subjects with type 2 diabetes, could be predisposing factors for type 2 diabetes. A combination of these two variants would more often lead to degenerative complications.