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Original Research Communication |
1 From the Departments of Clinical Biochemistry and Pediatrics, Research Centre, Ste-Justine Hospital, Université de Montréal, and the Institut de Recherches Cliniques de Montréal, Montreal Children's Hospital, McGill University, Montréal.
Background: Several studies have examined the association of the methylenetetrahydrofolate reductase (MTHFR) genotype with plasma homocysteine in adults, but few studies have been performed in children.
Objective: We measured the concentrations of plasma total homocysteine, folate, and vitamin B-12 in a group of healthy fasting children and related these to MTHFR genotype.
Design: After the subjects fasted, blood samples were collected into EDTA-containing tubes. Plasma, red blood cells, and the buffy coat were immediately stored at -80°C for biochemical and molecular analyses. Plasma total homocysteine was determined by HPLC. Folate and vitamin B-12 were measured by a double-labeled radioimmunoassay, and the genotypic analysis was performed by polymerase chain reaction amplification of genomic DNA extracted from blood leukocytes.
Results: Plasma homocysteine concentrations correlated negatively with folate and vitamin B-12, but positively with age (P < 0.0001). Whereas folate and vitamin B-12 accounted for 27% and 19% of the variation in homocysteine, respectively, age accounted for 48% of the variation. When the cohort was divided into older (>10 y) and younger (
10 y) individuals, folate was significantly lower in the older individuals who were homozygous for the mutation (T/T) than in those who were homozygous for the wild-type allele (C/C). Homocysteine was higher in the T/T group than in both the C/C and C/T subgroups aged >10 y.
Conclusion: Our data show that in a healthy pediatric population, MTHFR genotype played a significant role in determining homocysteine concentrations in older (>10 y), nutritionally stressed children.
Key Words: Homocysteine • methylenetetrahydrofolate reductase • MTHFR genotype • folate • vitamin B-12 • children
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