Genetic Variants in One-Carbon Metabolism and Their Effects on DHA Biomarkers in Pregnant Women: A Post-Hoc Analysis

• Published in: Nutrients Vol. 14; no. 18; p. 3801
• Main Authors: Loinard-González, Aura Alex P, Malysheva, Olga V, Klatt, Kevin C, Caudill, Marie A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-09-2022; MDPI
• Subjects: Analysis; Betaine-homocysteine S-methyltransferase; Bioavailability; Biological markers; Biomarkers; Carbon; Choline; DHA; Dietary supplements; Docosahexaenoic Acids; Fatty Acids; Female; Fetuses; Food and nutrition; Generalized linear models; Genes; Genetic aspects; Genetic diversity; Genetic research; Genetic variance; genetic variants; Genotype & phenotype; Genotypes; Health aspects; Humans; Infant, Newborn; Lecithin; Metabolism; Methylenetetrahydrofolate reductase; Methyltransferase; N-Methyltransferase; Omega-3 fatty acids; one-carbon metabolism; PEMT; Phosphatidylcholine; Phosphatidylcholines; Phosphatidylethanolamine; Phosphatidylethanolamine N-methyltransferase; Phosphatidylethanolamine N-Methyltransferase - genetics; Physiological aspects; Plasma; Pregnancy; Pregnant Women; Single nucleotide polymorphisms; Transferases; Vitamin B; United States; United States > US; genetic variants; choline; PEMT; DHA; one-carbon metabolism; pregnancy
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14183801

The delivery of docosahexanoic acid (DHA) to the fetus is dependent on maternal one-carbon metabolism, as the latter supports the hepatic synthesis and export of a DHA-enriched phosphatidylcholine molecule via the phosphatidylethanolamine N-methyltransferase (PEMT) pathway. The following is a post-hoc analysis of a choline intervention study that sought to investigate whether common variants in one-carbon metabolizing genes associate with maternal and/or fetal blood biomarkers of DHA status. Pregnant women entering their second trimester were randomized to consume, until delivery, either 25 (n = 15) or 550 (n = 15) mg choline/d, and the effects of genetic variants in the PEMT, BHMT, MTHFD1, and MTHFR genes on DHA status were examined. Variant (vs. non-variant) maternal PEMT rs4646343 genotypes tended to have lower maternal RBC DHA (% total fatty acids) throughout gestation (6.9% vs. 7.4%; main effect, p = 0.08) and lower cord RBC DHA at delivery (7.6% vs. 8.4%; main effect, p = 0.09). Conversely, variant (vs. non-variant) maternal MTHFD1 rs2235226 genotypes exhibited higher cord RBC DHA (8.3% vs. 7.3%; main effect, p = 0.0003) and higher cord plasma DHA (55 vs. 41 μg/mL; main effect, p = 0.05). Genotype tended to interact with maternal choline intake (p < 0.1) to influence newborn DHA status for PEMT rs4646343 and PEMT rs7946. These data support the need to consider variants in one-carbon metabolic genes in studies assessing DHA status and requirements during pregnancy.