The MTHFR 677C>T polymorphism is associated with unmetabolized folic acid in breast milk in a cohort of Canadian women. Issue 2 (21st April 2019)

• Record Type: Journal Article
• Authors: Page, Rachael; Wong, Alex; Arbuckle, Tye E; MacFarlane, Amanda J
• Is Part Of: American journal of clinical nutrition. Volume 110:Issue 2(2019)
• Page Start: 401
• Page End: 409
• Publication Date: 2019-04-21
• Subjects: folate -- unmetabolized folic acid -- breast milk -- supplements -- methylenetetrahydrofolate reductase -- methionine synthase -- methionine synthase reductase; Diet therapy -- Periodicals; Nutrition -- Periodicals; Dietetics -- Periodicals; 613.205
• DOI: 10.1093/ajcn/nqz056
• Languages: English
• ISSNs: 0002-9165

Abstract

ABSTRACT: Background: Maternal nutrition and genetics are determinants of breast-milk nutrient composition and, as such, are determinants of the nutritional exposure of breastfed infants. Objectives: The aim of this study was to determine whether common maternal single nucleotide polymorphisms (SNPs) in folate-dependent enzymes are associated with breast-milk folate content in a cohort of mothers enrolled in the Maternal–Infant Research on Environmental Chemicals (MIREC) study. Methods: The MIREC study is a Canadian prospective pregnancy cohort study that recruited 2001 participants between 2008 and 2011. Five folate-related SNPs— MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTHFR 1793G>A (rs2274976), MTR 2756A>G (rs1805087), and MTRR 66A>G (rs1801394)—were genotyped. Breast milk was sampled ∼1 mo postpartum, and tetrahydrofolate (THF), 5-methyl-THF, 5-formyl-THF, 5, 10-methenyl-THF, and unmetabolized folic acid (UMFA) were measured using liquid chromatography–tandem mass spectrometry in a subset of participants ( n = 551). Associations were assessed using Wald's test. Associations were considered significant if P ≤ 0.01 (Bonferroni correction for multiple testing). Results: None of the SNPs were associated with total breast-milk folate. However, the MTHFR 677C>T SNP was associated with breast-milk UMFA ( R 2 = 0.01; unadjusted P = 0.004), explaining a small portion of total variance; this association remained significant when adjusted for other covariates, including supplemental folic acid consumption. The MTHFR 1793G>A and MTRR 66A>G SNPs tended to be associated with 5-methyl-THF ( R 2 = 0.008, P = 0.04) and reduced folates (THF + 5-methyl-THF + 5-formyl-THF + 5, 10-methenyl-THF; R 2 = 0.01, P = 0.02), respectively. Conclusions: We found that total breast-milk folate content was not associated with any of the folate-related SNPs examined. The association between the MTHFR 677C>T SNP and breast-milk UMFA, albeit modest, highlights the need to better understand the determinants of breast-milk folate and the impact they might have on milk folate bioavailability.