Effects of unmetabolized folic acid on global DNA methylation, mRNA expression and NK cells cytotoxicity in individuals exposed to mandatory fortification with folic acid and / or therapeutic use of this vitamin

Abstract

Folic acid is a vitamin of B complex which plays an important role in several reactions in the body. Its deficiency produces several clinical complications, such as anemia, increase in cancer risk and cardiovascular disease, defects in neural tube formation, among others. However, with the onset of wheat and corn flour fortification with folic acid in Brazil, since 2004, the population began to be exposed to amounts of this vitamin, beyond that normally present in foods. Its known folic acid in synthetic form cannot be completely metabolized leading to the appearance of a unmetabolized fraction in the body. This is more worrying in individuals who beyond fortification food take therapeutic use of this vitamin, such as those with beta-thalassaemic trait and hereditary spherocytosis. The aim of this study will be assess whether serum concentration of unmetabolized folic acid affect the global methylation, mRNA expression of beta-globin, interferon-gamma, TNF-alpha, interleukin-8, MTHFR and DHFR in mononuclear leukocytes and cytotoxicity of NK cells in 30 patients with hereditary spherocytosis and 100 patients with beta-thalassaemic trait exposed to mandatory fortification and use of 5 mg/day of folic acid, from the Hematology Clinical by Universidade Federal de São Paulo - UNIFESP, Santa Casa de Misericórdia de São Paulo Clinical and 260 healthy individuals exposed to mandatory fortification from the Universidade de São Paulo and UNIFESP. (AU)