Details

Autor(en) / Beteiligte

• Yang, Quan-He
• Botto, Lorenzo D
• Gallagher, Margaret
• Friedman, JM
• Sanders, Christopher L
• Koontz, Deborah
• Nikolova, Stanimila
• Erickson, J. David
• Steinberg, Karen

Titel

Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: findings from the third National Health and Nutrition Examination Survey DNA Bank

Ist Teil von

• The American journal of clinical nutrition, 2008-07, Vol.88 (1), p.232-246

Ort / Verlag

Bethesda, MD: American Society for Nutrition

Erscheinungsjahr

2008

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• BACKGROUND: Abnormalities of folate and homocysteine metabolism are associated with a number of pediatric and adult disorders. Folate intake and genetic polymorphisms encoding folate-metabolizing enzymes influence blood folate and homocysteine concentrations, but the effects and interactions of these factors have not been studied on a population-wide basis. OBJECTIVE: The objective was to assess the prevalence of these genetic polymorphisms and their relation to serum folate and homocysteine concentrations. DESIGN: DNA samples from 6793 participants in the third National Health and Nutrition Examination Survey (NHANES III) during 1991-1994 were genotyped for polymorphisms of genes coding for folate pathway enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C[rightward arrow]T and 1298A[rightward arrow]C, methionine synthase reductase (MTRR) 66A[rightward arrow]G, and cystathionine-β-synthase 844ins68. The influence of these genetic variants on serum folate and homocysteine concentrations was analyzed by age, sex, and folate intake in 3 race-ethnicity groups. RESULTS: For all race-ethnicity groups, serum folate and homocysteine concentrations were significantly related to the MTHFR 677C[rightward arrow]T genotype but not to the other polymorphisms. Persons with the MTHFR 677 TT genotype had a 22.1% (95% CI: 14.6%, 28.9%) lower serum folate and a 25.7% (95% CI: 18.6%, 33.2%) higher homocysteine concentration than did persons with the CC genotype. Moderate daily folic acid intake (mean: 150 μg/d; 95% CI: 138, 162) significantly reduced the difference in mean homocysteine concentrations between those with the MTHFR 677 CC and TT genotypes. We found a significant interaction between MTHFR 677C[rightward arrow]T and MTRR 66A[rightward arrow]G on serum homocysteine concentrations among non-Hispanic whites. CONCLUSIONS: The MTHFR 677C[rightward arrow]T polymorphism was associated with significant differences in serum folate and homocysteine concentrations in the US population before folic acid fortification. The effect of MTHFR 677C[rightward arrow]T on homocysteine concentrations was reduced by moderate daily folic acid intake.