MTHFR C677T genotype influences the isotopic enrichment of one-carbon metabolites in folate-compromised men consuming d9-choline.
BACKGROUND
Homozygosity for the variant 677T allele in the methylenetetrahydrofolate reductase (MTHFR) gene increases the requirement for folate and may alter the metabolic use of choline. The choline adequate intake is 550 mg/d for men, although the metabolic consequences of consuming extra choline are unclear.


OBJECTIVE
Deuterium-labeled choline (d9-choline) as tracer was used to determine the differential effects of the MTHFR C677T genotype and the effect of various choline intakes on the isotopic enrichment of choline derivatives in folate-compromised men.


METHODS
Mexican American men with the MTHFR 677CC or 677TT genotype consumed a diet providing 300 mg choline/d plus supplemental choline chloride for total choline intakes of 550 (n = 11; 4 with 677CC and 7 with 677TT) or 1100 (n = 12; 4 with 677CC and 8 with 677TT) mg/d for 12 wk. During the last 3 wk, 15% of the total choline intake was provided as d9-choline.


RESULTS
Low but measurable enrichments of the choline metabolites were achieved, including that of d3-phosphatidylcholine (d3-PtdCho)--a metabolite produced in the de novo pathway via choline-derived methyl groups. Men with the MTHFR 677TT genotype had a higher urinary enrichment ratio of betaine to choline (P = 0.041), a higher urinary enrichment of sarcosine (P = 0.041), and a greater plasma enrichment ratio of d9-betaine to d9-PtdCho with the 1100 mg choline/d intake (P = 0.033).


CONCLUSIONS
These data show for the first time in humans that choline itself is a source of methyl groups for de novo PtdCho biosynthesis and indicate that the MTHFR 677TT genotype favors the use of choline as a methyl donor.
Division of Nutritional Sciences and Genomics, Cornell University, Ithaca, NY 14853, USA.
Jian
J
Yan
Wei
W
Wang
Jesse F
JF
Gregory
Olga
O
Malysheva
J Thomas
JT
Brenna
Sally P
SP
Stabler
Robert H
RH
Allen
Marie A
MA
Caudill
D000293:Adolescent; D000328:Adult; D001622:Betaine / Q000097:blood / Q000652:urine; D002794:Choline / Q000008:administration & dosage / Q000378:metabolism*; D003903:Deuterium / Q000008:administration & dosage / Q000378:metabolism; D019587:Dietary Supplements; D005494:Folic Acid Deficiency / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D008745:Methylation; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D017058:Mexican Americans; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000096:biosynthesis; D012521:Sarcosine / Q000652:urine; D013194:Staining and Labeling; D055815:Young Adult
D010713:Phosphatidylcholines; D001622:Betaine; D003903:Deuterium; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002794:Choline; D012521:Sarcosine