Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B-12, and folate status on plasma homocysteine in children

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Abstract
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.