title: Methylenetetrahydrofolate reductase mutation (677C-->T) negatively influences plasma homocysteine response to marginal folate intake in elderly women.
abstract: Individuals who are homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C --> T mutation have depressed serum folate (SF) and elevated plasma total homocysteine (tHcy) concentrations, which may affect folate requirements and increase the risk for coronary artery disease. A controlled metabolic study (14 weeks) using a depletion/repletion protocol was performed in women (aged 60 to 85 years, N = 33) to provide age-specific data on the effects of the MTHFR mutation on SF and tHcy status. Subjects consumed a moderately folate-deplete diet (118 microg/d) for 7 weeks, followed by 7 weeks of folate repletion with 200 or 415 microg/d provided as two different treatments. Following folate depletion, the mean SF concentration was lower for homozygous (P = .017) versus heterozygous subjects. Homozygotes for the 677C --> T mutation showed a higher (P = .015) percent increase in plasma tHcy (44%) than heterozygous (20%) or normal (15%) subjects. At week 7, the mean plasma tHcy concentration was higher in homozygous subjects (12.5 +/- 5.3 micromol/L, mean +/- SD) versus the heterozygous (10.8 +/- 3.8 micromol/L, P = .008) or normal (11.3 +/- 2.7 micromol/L, P = .001) genotype groups. Following folate repletion, plasma tHcy concentrations were not different between genotype groups, despite a higher (P < .016) SF concentration in subjects with the homozygous genotype. These data suggest that older women who are homozygous for the MTHFR 677C --> T mutation may be at risk for greater elevations in plasma tHcy in response to moderately low folate intake as compared with individuals with the normal or heterozygous genotypes.
authors.affiliation: Food Science and Human Nutrition Department, College of Agricultural and Life Sciences, University of Florida, Gainesville 32611-0370, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: Kauwell
authors.forename: C E
authors.initials: CE
authors.lastname: Wilsky
authors.forename: J J
authors.initials: JJ
authors.lastname: Cerda
authors.forename: K
authors.initials: K
authors.lastname: Herrlinger-Garcia
authors.forename: A D
authors.initials: AD
authors.lastname: Hutson
authors.forename: D W
authors.initials: DW
authors.lastname: Theriaque
authors.forename: A
authors.initials: A
authors.lastname: Boddie
authors.forename: G C
authors.initials: GC
authors.lastname: Rampersaud
authors.forename: L B
authors.initials: LB
authors.lastname: Bailey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)