Lymphocyte DNA strand breakage declines in Mexican American men with the MTHFR 677TT genotype in a folate deplete environment

Abstract

This study sought to ascertain the influences of declining folate stores, MTHFR C677T genotype, and varying choline intakes on biomarkers of lymphocyte DNA damage in Mexican American men (n=30) with the MTHFR 677CC (n=11) or TT (n=19) genotype under conditions of controlled nutrient intake. For each subject, lymphocyte DNA damage was assessed at wk 0 and 12 by use of the Comet Assay (single cell gel electrophoresis) and four derived parameters including percentage tail DNA, tail length, extent tail moment and olive tail moment. Although no main effects of the independent variables were detected on metrics of DNA damage, the response of the tail moments to declining folate status tended to differ between the MTHFR genotypes (time × genotype, P=0.08–0.10). Upon stratifying the data by MTHFR C677T genotype, declines (P< 0.05) in all four Comet‐derived DNA damage parameters were observed in men with the 677TT genotype whereas no changes (P>0.73) were observed in the 677CC genotype. These data suggest that a reduction in MTHFR activity in Mexican American men with the MTHFR 677TT genotype poses an advantage of decreased DNA strand breakage possibly by directing more folate to participate in nucleotide biosynthesis reactions. Supported by NIH #S06GM053933 and funds from the California Agricultural Research Initiative.