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- W2896232842 abstract "Genetic polymorphisms can explain some of the population- and individual-based variations in nutritional status biomarkers. We sought to screen the entire human genome for common genetic polymorphisms that influence folate-status biomarkers in healthy individuals. 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. 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. 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." @default.
- W2896232842 created "2018-10-26" @default.
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- W2896232842 date "2018-12-01" @default.
- W2896232842 modified "2023-09-26" @default.
- W2896232842 title "The 677C→T variant of MTHFR is the major genetic modifier of biomarkers of folate status in a young, healthy Irish population" @default.
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- W2896232842 doi "https://doi.org/10.1093/ajcn/nqy209" @default.
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