MTHFR gene polymorphisms in diabetes mellitus

The methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) are three regulatory enzymes in the folic acid (FA) cycle play a critical role in the balance of methionine and homocysteine. MTHFR and MTRR gene polymorphisms affect the biochemical activities of enzymes, impairing the remethylation of homocysteine to methionine. In 1972, severe MTHFR deficiency resulting in homocystinuria was first reported, suggesting MTHFR involvement in the disease. MTHFR C677T polymorphism can independently increase the risk of high homocysteine (HHcy) in plasma. Elevation of homocysteine levels could increase the risk of microvascular damage, thrombosis, heart disease, etc. Vascular complications were regarded as a leading major cause of diabetes mortality, and disability increases individual health and economic burden. Diabetes mellitus (DM) is a chronic inflammatory disease, and conventional medications do not provide a complete cure for diabetes. It was essential to identify other risk factors for the intervention and prevention of diabetes. MTHFR gene polymorphism is an emerging risk factor in diabetes. Recent studies have shown that polymorphisms of the MTHFR gene play a significant role in the pathophysiology of diabetes, including inflammation and insulin resistance. This review summarizes the association between MTHER gene polymorphism and diabetes.