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Phenotypic expression of the methylenetetrahydrofolate reductase 677C-->T polymorphism and flavin cofactor
Steinar Hustad1, Bjørn G Nedrebø, Per Magne Ueland
1LOCUS for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway. steinar.hustad@farm.uib.no
Background:
The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) 677C-->T polymorphism modifies the risk of coronary artery disease and colon cancer and is related to plasma concentrations of total homocysteine (tHcy). Riboflavin status modifies the metabolic effect of the polymorphism, and thyroid hormones increase the synthesis of flavin cofactors.
Objective:
The aim of the study was to investigate the phenotypic expression of the MTHFR 677C-->T polymorphism in terms of plasma tHcy concentrations in patients with thyroid dysfunction.
Design:
The study population consisted of 182 patients with hyperthyroidism. We studied plasma tHcy in relation to MTHFR genotype, riboflavin, and folate before and during 6 mo of treatment with antithyroid drugs.
Results:
Before treatment, tHcy was higher in patients with the mutant enzyme than in those with the wild-type enzyme. A genotype effect was observed only at low riboflavin or folate concentrations (P
Conclusion:
Thyroid status affects the phenotypic expression of the MTHFR 677C-->T polymorphism, possibly by modifying the availability of flavin cofactors.