The 677C?T variant of MTHFR is the major genetic modifier of biomarkers of folate status in a young, healthy Irish population.

ABSTRACT: Background:Genetic polymorphisms can explain some of the population- and individual-based variations in nutritional status biomarkers. Objective:We sought to screen the entire human genome for common genetic polymorphisms that influence folate-status biomarkers in healthy individuals. Design:We carried out candidate gene analyses and genome-wide association scans in 2232 young, healthy Irish subjects to evaluate which common genetic polymorphisms influence red blood cell folate, serum folate, and plasma total homocysteine. Results:The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C?T (rs1801133) variant was the major genetic modifier of all 3 folate-related biomarkers in this Irish population and reached genome-wide significance for red blood cell folate (P = 1.37 × 10-17), serum folate (P = 2.82 × 10-11), and plasma total homocysteine (P = 1.26 × 10-19) concentrations. A second polymorphism in the MTHFR gene (rs3753584, P = 1.09 × 10-11) was the only additional MTHFR variant to exhibit any significant independent effect on red blood cell folate. Other MTHFR variants, including the 1298A?C variant (rs1801131), appeared to reach genome-wide significance, but these variants shared linkage disequilibrium with MTHFR 677C?T and were not significant when analyzed in MTHFR 677CC homozygotes. No additional non-MTHFR modifiers of red blood cell or plasma folate were detected. Two additional genome-wide significant modifiers of plasma homocysteine were found in the region of the dipeptidase 1 (DPEP1) gene on chromosome 16 and the Twist neighbor B (TWISTNB) gene on chromosome 7. Conclusions:The MTHFR 677C?T variant is the predominant genetic modifier of folate status biomarkers in this healthy Irish population. It is not necessary to determine MTHFR 677C?T genotype to evaluate folate status because its effect is reflected in concentrations of standard folate biomarkers. The MTHFR 1298A?C variant had no independent effect on folate status biomarkers. To our knowledge, this is the first genome-wide association study report on red blood cell folate and the first report of an association between homocysteine and TWISTNB.

SUBMITTER: Shane B 

PROVIDER: S-EPMC6290363 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature