John T Brosnan1, James L Mills2, Per M Ueland3, Barry Shane4, Ruzong Fan5, Chi-Yang Chiu6, Faith Pangilinan7, Lawrence C Brody7, Margaret E Brosnan1, Theerawat Pongnopparat1, Anne M Molloy8,9. 1. Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. 2. Epidemiology Branch. 3. Section of Pharmacology, Institute of Medicine, University of Bergen and Haukeland University Hospital, Bergen, Norway. 4. Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, CA. 5. Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC. 6. Biostatistics and Bioinformatics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD. 7. Molecular Pathogenesis Section, Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD. 8. Medicine and Biochemistry and Immunology, Trinity College Dublin, Ireland. 9. Biochemistry and Immunology, Trinity College Dublin, Ireland.
Abstract
Background: Formate is an important metabolite that serves as a donor of one-carbon groups to the intracellular tetrahydrofolate pool. However, little is known of its circulating concentrations or of their determinants. Objective: This study aimed to define formate concentrations and their determinants in a healthy young population. Design: Serum formate was measured in 1701 participants from the Trinity Student Study. The participants were men and women, aged 18 to 28 y, enrolled at Trinity College, Dublin. Formate concentrations were compared with other one-carbon metabolites, vitamin status, potential formate precursors, genetic polymorphisms, and lifestyle factors. Results: Serum formate concentrations ranged from 8.7 to 96.5 µM, with a mean of 25.9 µM. Formate concentrations were significantly higher in women than in men; oral contraceptive use did not further affect them. There was no effect of smoking or of alcohol ingestion, but the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) 677C→T (rs1801133) polymorphism was associated with a significantly decreased formate concentration. Formate was positively associated with potential metabolic precursors (serine, methionine, tryptophan, choline) but not with glycine. Formate concentrations were positively related to serum folate and negatively related to serum vitamin B-12. Conclusions: Formate concentrations were sensitive to the concentrations of metabolic precursors. In view of the increased susceptibility of women with the TT genotype of MTHFR to give birth to infants with neural tube defects as well as the effectiveness of formate supplementation in decreasing the incidence of folate-resistant neural tube defects in susceptible mice, it will be important to understand how this genotype decreases the serum formate concentration. This trial was registered at www.clinicaltrials.gov as NCT03305900.
Background: Formate is an important metabolite that serves as a donor of one-carbon groups to the intracellular tetrahydrofolate pool. However, little is known of its circulating concentrations or of their determinants. Objective: This study aimed to define formate concentrations and their determinants in a healthy young population. Design: Serum formate was measured in 1701 participants from the Trinity Student Study. The participants were men and women, aged 18 to 28 y, enrolled at Trinity College, Dublin. Formate concentrations were compared with other one-carbon metabolites, vitamin status, potential formate precursors, genetic polymorphisms, and lifestyle factors. Results: Serum formate concentrations ranged from 8.7 to 96.5 µM, with a mean of 25.9 µM. Formate concentrations were significantly higher in women than in men; oral contraceptive use did not further affect them. There was no effect of smoking or of alcohol ingestion, but the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) 677C→T (rs1801133) polymorphism was associated with a significantly decreased formate concentration. Formate was positively associated with potential metabolic precursors (serine, methionine, tryptophan, choline) but not with glycine. Formate concentrations were positively related to serum folate and negatively related to serum vitamin B-12. Conclusions: Formate concentrations were sensitive to the concentrations of metabolic precursors. In view of the increased susceptibility of women with the TT genotype of MTHFR to give birth to infants with neural tube defects as well as the effectiveness of formate supplementation in decreasing the incidence of folate-resistant neural tube defects in susceptible mice, it will be important to understand how this genotype decreases the serum formate concentration. This trial was registered at www.clinicaltrials.gov as NCT03305900.
Authors: Simon G Lamarre; Anne M Molloy; Stacey N Reinke; Brian D Sykes; Margaret E Brosnan; John T Brosnan Journal: Am J Physiol Endocrinol Metab Date: 2011-09-20 Impact factor: 4.310
Authors: Oana M Deac; James L Mills; Barry Shane; Øivind Midttun; Per M Ueland; John T Brosnan; Margaret E Brosnan; Eamon Laird; Eileen R Gibney; Ruzong Fan; Yifan Wang; Lawrence C Brody; Anne M Molloy Journal: J Nutr Date: 2015-02-18 Impact factor: 4.798
Authors: James L Mills; Tonia C Carter; John M Scott; James F Troendle; Eileen R Gibney; Barry Shane; Peadar N Kirke; Per M Ueland; Lawrence C Brody; Anne M Molloy Journal: Am J Clin Nutr Date: 2011-06-08 Impact factor: 7.045
Authors: Shannon E Washburn; Marie A Caudill; Olga Malysheva; Amanda J MacFarlane; Nathalie A Behan; Brian Harnett; Luke MacMillan; Theerawat Pongnopparat; John T Brosnan; Margaret E Brosnan Journal: Am J Physiol Endocrinol Metab Date: 2015-03-24 Impact factor: 4.310
Authors: Steven R Davis; Peter W Stacpoole; Jerry Williamson; Lilia S Kick; Eoin P Quinlivan; Bonnie S Coats; Barry Shane; Lynn B Bailey; Jesse F Gregory Journal: Am J Physiol Endocrinol Metab Date: 2003-10-14 Impact factor: 4.310
Authors: Anne M Molloy; Faith Pangilinan; James L Mills; Barry Shane; Mary B O'Neill; David M McGaughey; Aneliya Velkova; Hatice Ozel Abaan; Per M Ueland; Helene McNulty; Mary Ward; J J Strain; Conal Cunningham; Miriam Casey; Cheryl D Cropp; Yoonhee Kim; Joan E Bailey-Wilson; Alexander F Wilson; Lawrence C Brody Journal: Am J Hum Genet Date: 2016-04-28 Impact factor: 11.025
Authors: John T Brosnan; Lesley Plumptre; Margaret E Brosnan; Theerawat Pongnopparat; Shannon P Masih; Carly E Visentin; Howard Berger; Yvonne Lamers; Marie A Caudill; Olga V Malysheva; Deborah L O'Connor; Young-In Kim Journal: Am J Clin Nutr Date: 2019-11-01 Impact factor: 7.045