Hea Jin Park1, Lynn B Bailey2, Deanna C Shade2, Dorothy B Hausman2, Natalie M Hohos2, Richard B Meagher3, Gail Pa Kauwell4, Richard D Lewis2, Alicia K Smith5. 1. Department of Foods and Nutrition, University of Georgia, Athens, GA, USA. Electronic address: hjpark@uga.edu. 2. Department of Foods and Nutrition, University of Georgia, Athens, GA, USA. 3. Department of Genetics, University of Georgia, Athens, GA, USA. 4. Food Science and Human Nutrition Department, University of Florida, Gainesville, FL, USA. 5. Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
Abstract
BACKGROUND/ OBJECTIVES: Obesity and maternal folate deficiency are associated with increased risk for neural tube defects (NTDs). Limited knowledge exists on the impact of folate status or obesity on DNA methylation of genes related to NTD risk and folate metabolism. SUBJECTS/ METHODS: Women (18-35y) with normal weight (NW; BMI 18.5-24.9kg/m2; n=12) and obesity (OB; BMI >30kg/m2; n=6) were provided FA (800μg/d) for 8-weeks. Serum folate concentration and changes in DNA methylation across 2098 CpG sites in 91 genes related to NTD risk and folate metabolism were examined. RESULTS: Serum folate concentration increased in both groups following FA supplementation, but OB maintained a relative lower concentration (NW; 38.36±2.50-71.41±3.02nmol/L and OB; 27.12±3.09-56.85±3.90nmol/L). Methylation of 56 and 99 CpG sites changed in response to supplementation in NW and OB, respectively, and majority of these sites decreased in methylation in both groups. Only 4 CpG sites responded to supplementation in both groups. Gene ontology analysis revealed a response to supplementation in 61 biological processes (BPs) from the selected genes. Five of the 61 BPs were identified only in NW, including neural tube closure, while 13 of the 61 BPs were enriched only in OB, including folate metabolism, vitamin B12 metabolism and methylation related processes. CONCLUSIONS: Changes in DNA methylation in genes related to NTD risk and folate metabolism in response to FA supplementation were different in NW and OB. Increased NTD risk and abnormal folate metabolism in obesity may be due to a distinctive epigenetic response to folate status in these genes. Published by Elsevier Ltd.
BACKGROUND/ OBJECTIVES:Obesity and maternal folate deficiency are associated with increased risk for neural tube defects (NTDs). Limited knowledge exists on the impact of folate status or obesity on DNA methylation of genes related to NTD risk and folate metabolism. SUBJECTS/ METHODS:Women (18-35y) with normal weight (NW; BMI 18.5-24.9kg/m2; n=12) and obesity (OB; BMI >30kg/m2; n=6) were provided FA (800μg/d) for 8-weeks. Serum folate concentration and changes in DNA methylation across 2098 CpG sites in 91 genes related to NTD risk and folate metabolism were examined. RESULTS: Serum folate concentration increased in both groups following FA supplementation, but OB maintained a relative lower concentration (NW; 38.36±2.50-71.41±3.02nmol/L and OB; 27.12±3.09-56.85±3.90nmol/L). Methylation of 56 and 99 CpG sites changed in response to supplementation in NW and OB, respectively, and majority of these sites decreased in methylation in both groups. Only 4 CpG sites responded to supplementation in both groups. Gene ontology analysis revealed a response to supplementation in 61 biological processes (BPs) from the selected genes. Five of the 61 BPs were identified only in NW, including neural tube closure, while 13 of the 61 BPs were enriched only in OB, including folate metabolism, vitamin B12 metabolism and methylation related processes. CONCLUSIONS: Changes in DNA methylation in genes related to NTD risk and folate metabolism in response to FA supplementation were different in NW and OB. Increased NTD risk and abnormal folate metabolism in obesity may be due to a distinctive epigenetic response to folate status in these genes. Published by Elsevier Ltd.
Authors: Yohanna de Oliveira; Raquel Patrícia Ataíde Lima; Rafaella Cristhine Pordeus Luna; Mussara Gomes Cavalcanti Alves Monteiro; Cássia Surama Oliveira da Silva; Rayner Anderson Ferreira do Nascimento; Keylha Querino de Farias Lima; Ana Hermínia Andrade E Silva; Flávia Emília Leite de Lima Ferreira; Rodrigo Pinheiro de Toledo Vianna; Ronei Marcos de Moraes; Naila Francis Paulo de Oliveira; Aléssio Tony Cavalcanti de Almeida; Alexandre Sérgio Silva; Alcides da Silva Diniz; Maria José de Carvalho Costa; Maria da Conceição Rodrigues Gonçalves Journal: J Transl Med Date: 2018-06-05 Impact factor: 5.531