Role of metabolizing MTHFR gene polymorphism (rs1801133) and its mRNA expression among Type 2 Diabetes

Type 2 Diabetes is a glucose metabolic disorder occurred by insulin insensitivity in which folate metabolism plays an important role. it is believed that polymorphism of Methylenetetrahydrofolate reductase (MTHFR) C677T linked with type 2 diabetes mellitus. However, results are conflicted. therefore, in this study we re-examine the relationship between MTHFR C677T in type 2 diabetes mellitus patients.

Present research work included 100 newly diagnosed type 2 diabetic mellitus (T2DM) cases and 100 healthy individuals. After the blood sample collection all the biochemical parameters were evaluated among the T2DM cases and healthy individuals. DNA and RNA extraction from whole blood was done to study the MTHFR gene polymorphism by allele specific polymerase chain reaction method and its expression analysis was done by quantitative real time polymerase chain reaction method.

The significant difference was observed in genotype distribution among case and control group (p=0.0002). Compared with wildtype CC genotype, CT heterozygous (OR=2.95, 95% Cl=1.62-5.38) and TT homozygous (OR=3.20, CI=1.79-5.73) suggest to have effect of MTHFR polymorphism on type 2 mellitus risk. Moreover, relative MTHFR mRNA expression was found for wild type CC genotype 3.02-fold, CT heterozygous genotype 2.57 fold and mutant TT homozygous genotype 0.50-fold which is down regulated (p<0.0001).

Our results indicates that the polymorphism in MTHFR C677T plays significant role in type II diabetes risk. MTHFR CT heterozygous and mutant TT genotype showed reduced mRNA expression among the T2DM patients. However, large scale case-control studies are needed to strengthen such conclusion in the future.