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. 2007 May;80(5):846-55.
doi: 10.1086/513520. Epub 2007 Mar 13.

The methylenetetrahydrofolate reductase 677C-->T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism

Steinar Hustad  1 , Øivind Midttun, Jørn Schneede, Stein Emil Vollset, Tom Grotmol, Per Magne Ueland
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The methylenetetrahydrofolate reductase 677C-->T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism

Steinar Hustad et al. Am J Hum Genet. .
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Abstract

Folates are carriers of one-carbon units and are metabolized by 5,10-methylenetetrahydrofolate reductase (MTHFR) and other enzymes that use riboflavin, cobalamin, or vitamin B6 as cofactors. These B vitamins are essential for the remethylation and transsulfuration of homocysteine, which is an important intermediate in one-carbon metabolism. We studied the MTHFR 677C-->T polymorphism and B vitamins as modulators of one-carbon metabolism in 10,601 adults from the Norwegian Colorectal Cancer Prevention (NORCCAP) cohort, using plasma total homocysteine (tHcy) as the main outcome measure. Mean concentrations of plasma tHcy were 10.4 micromol/liter, 10.9 micromol/liter, and 13.3 micromol/liter in subjects with the CC (51%), CT (41%), and TT (8%) genotypes, respectively. The MTHFR 677C-->T polymorphism, folate, riboflavin, cobalamin, and vitamin B6 were independent predictors of tHcy in multivariate models (P<.001 and genotype effects were strongest when b vitamins low conversely the mthfr polymorphism influenced vitamin which in tt group estimated thcy difference between subjects with concentrations lowest compared highest quartile was micromol for folate riboflavin cobalamin b6. furthermore interactions observed more strongly related to plasma of other low. study provides comprehensive data on mthfr-b network has major transfer one-carbon units. individuals particularly sensitive status several might be candidates personalized nutritional recommendations.>

Figures

Figure 1.
B vitamins as determinants of plasma tHcy according to folate concentrations and MTHFR 677C→T genotype. The population was stratified according to levels of serum folate (below and above the median) and MTHFR 677C→T genotype. The riboflavin-tHcy, cobalamin-tHcy, and vitamin B6–tHcy relationships were then studied in a regression model, which included these vitamins in addition to sex, age, creatinine, and study center. Means with upper limits of 95% CIs and P for trend across quartiles are shown in each panel. Nutrient-gene interaction terms were calculated as the product between MTHFR genotype and the various B vitamins.
Figure 2.
B vitamins as determinants of plasma tHcy according to riboflavin concentrations and MTHFR 677C→T genotype. The population was stratified according to levels of plasma riboflavin (below and above the median) and MTHFR 677C→T genotype. The folate-tHcy, cobalamin-tHcy, and vitamin B6–tHcy relationships were then studied in a regression model, which included these vitamins in addition to sex, age, creatinine, and study center. Means with upper limits of 95% CIs and P for trend across quartiles are shown in each panel. Nutrient-gene interaction terms were calculated as the product between MTHFR genotype and the various B vitamins.
Figure 3.
B vitamins as determinants of plasma tHcy according to cobalamin concentrations and MTHFR 677C→T genotype. The population was stratified according to levels of serum cobalamin (below and above the median) and MTHFR 677C→T genotype. The folate-tHcy, riboflavin-tHcy, and vitamin B6–tHcy relationships were then studied in a regression model, which included these vitamins in addition to sex, creatinine, and study center. Means with upper limits of 95% CIs and P for trend across quartiles are shown in each panel. Nutrient-gene interaction terms were calculated as the product between MTHFR genotype and the various B vitamins.
Figure  4.
Figure  4.
B vitamins as determinants of plasma tHcy according to vitamin B6 concentrations and MTHFR 677C→T genotype. The population was stratified according to levels of plasma vitamin B6 (below and above the median) and MTHFR 677C→T genotype. The folate-tHcy, riboflavin-tHcy, and cobalamin-tHcy relationships were then studied in a regression model, which included these vitamins in addition to sex, age, creatinine, and study center. Means with upper limits of 95% CIs and P for trend across quartiles are shown in each panel. Nutrient-gene interaction terms were calculated as the product between MTHFR genotype and the various B vitamins.
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