Genetic Factors Influence Choline Dynamics in Pregnant and Lactating Women

Single nucleotide polymorphisms (SNPs) can influence disease risk and alter choline requirements. Adequate choline intake is critical during pregnancy and lactation to ensure proper fetal and infant development. Using stable isotope methodology, this long‐term, randomized controlled feeding trial examined the impact of genetic variation in choline‐ and one‐carbon‐metabolizing enzymes on plasma choline dynamics. Pregnant, lactating, and control women consumed 480 or 930 mg choline/d for 10‐12 weeks; d9‐choline, which comprised 20% of total intake, was used as the metabolic tracer. Plasma enrichment of deuterated choline metabolites at study week 9 was measured by LCMS/MS. MTHFD1 rs2236225 genotype was found to interact with reproductive state and choline intake to influence plasma enrichment of choline metabolite ratios of d9 betaine: d9‐PTC (3‐way interaction, p = 0.012); d6‐DMG: d9‐betaine (reproductive state: genotype interaction, p = 0.050); d3‐choline: d9‐choline (3‐way interaction, p = 0.018); and d3+d6‐PTC: d9‐PTC (3‐way interaction, p = 5.1 x 10 ‐5 ). Additionally, individuals with one or more copies of the MTHFR rs1801133 variant allele had higher d6‐DMG: d9‐betaine enrichment (p = 0.0090), indicating that decreased activity of MTHFR may increase the utilization of choline‐derived methyl groups for the re‐methylation of homocysteine to methionine. These results indicate that genotype, reproductive state, and choline intake level interact to influence the metabolic flux of dietary choline. These data can inform choline intake recommendations for genetic‐subgroups of women differing in reproductive status.