G1793A polymorphisms in the methylene-tetrahydrofolate gene: effect of folic acid on homocysteine levels

Abstract

Mutations or polymorphisms in the gene of the enzyme methylenetetrahydrofolate (MTHFR) are associated with hyperhomocysteinemia and possibly with an elevated risk for vascular diseases. A study was conducted on 83 individuals with type 2 diabetes in order to determine the allelic and genotypic frequencies of the G1793A mutation and to assess the effect of folic acid supplementation on plasma homocysteine concentrations. The patients were attended by the Diabetes and Hypertension Program--Balneario Camboriu/SC and received daily supplements containing 1 mg of folic acid for 3 months. DNA was previously extracted from leukocytes and the G1793A mutation was detected by PCR-RFLP. Blood samples were collected during the basal period and after supplementation for the determination of homocysteine by HPLC, and of folic acid and vitamin B(12) by RIA. The allele frequency for the G1793A mutation was 3.01% and no homozygous individuals with mutant alleles were detected. Hyperhomocysteinemia was diagnosed in 27.71% of the patients, folic acid deficiency in 15.66%, and vitamin B(12) deficiency in 7.23%. Plasma homocysteine concentrations were inversely correlated with folic acid (r = -0.27, p = 0.01) and vitamin B(12) (r = -0.21; p = 0.05) concentrations. The individuals with a heterozygous genotype for the G1793A mutation showed borderlines or deficient values in folic acid and vitamin B(12) concentrations compared to individuals with a normal genotype. Hyperhomocysteinemia and the vitamin deficiencies presented by type 2 diabetic individuals, included with a heterozygous genotype for the G1793A mutation in the MTHFR gene, reached normal values by daily folic acid supplementation.