Methyl-Donors and EpiGenetics in The Gambia

NCT01811641 | Completed

• 1 other identifier: MRC-ING-MDEG
• Study Type: observational
• Target: 166
• Locations: 0 countries
• Sites: N/A

Brief Summary

Accumulating evidence suggests that early-life nutrition can affect metabolism and thus increase the risk of disease in adulthood (e.g. type II diabetes and obesity). One possible mechanism to explain these effects is epigenetic variation at critical periods of development. Epigenetic variation describes non-inherited permanent alterations to an individuals DNA. Recent work in mouse models has demonstrated that maternal nutritional status can affect such epigenetic processes such as DNA methylation and gene expression during embryonic development, with profound effects on outcomes. The investigators aim to study these processes in humans for the first time. The investigators will exploit the "experiment of nature" setting in The Gambia, i.e. fluctuation in diet according to season. During the 'hungry' season diets are known to be depleted in nutrients required for epigenetic gene regulation. Nutritional biomarkers in blood as well as the dietary intake will be measured in pregnant women according to season. A blood sample will also be taken from babies born to these women to determine whether there is a direct effect of diet on mothers' nutritional status and hence variation in DNA methylation patterns in their babies by season.

Conditions

Aberrant DNA Methylation

Keywords

season of conception; maternal nutritional status; infant DNA methylation

Outcome Measures

Primary Outcomes (1)

• DNA methylation of infants

  Measurement of DNA methylation of infants recruited into the study, at 3-6 months of age. Measurement of blood biomarkers monthly after dietary assessment or in early pregnancy

  infants: at 3-6 months of age

Secondary Outcomes (1)

• Blood biomarker status of women

  monthly for 12 months or in early pregnancy

Study Arms (1)

maternal methyl-donors, infant epigenetics

women of reproductive age in rural Gambia, infants born to these women

Other: season, dietary intake

Interventions

season, dietary intake OTHER

maternal methyl-donors, infant epigenetics

Eligibility Criteria

• Age: 1 Day - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

women of reproductive age in rural Gambia and their infants

You may qualify if:

• \- women aged 18-45 years on 15th March 2009, resident in West Kiang

You may not qualify if:

• on contraception
• confirmed pregnancy at recruitment
• enrolment in any study other than the ENID (Early Nutrition and Immune Development) trial (ISRCTN49285450)
• suffering from severe anaemia (haemoglobin \<7 g/dl) or known sickle cell disease
• \- born to the above women
• \- those known to be severely malnourished (weight-for-height Z-score \< -3)

Sponsors & Collaborators

• Medical Research Council: lead

Related Publications (3)

• Dominguez-Salas P, Moore SE, Baker MS, Bergen AW, Cox SE, Dyer RA, Fulford AJ, Guan Y, Laritsky E, Silver MJ, Swan GE, Zeisel SH, Innis SM, Waterland RA, Prentice AM, Hennig BJ. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun. 2014 Apr 29;5:3746. doi: 10.1038/ncomms4746.

  PMID: 24781383 RESULT

• Silver MJ, Kessler NJ, Hennig BJ, Dominguez-Salas P, Laritsky E, Baker MS, Coarfa C, Hernandez-Vargas H, Castelino JM, Routledge MN, Gong YY, Herceg Z, Lee YS, Lee K, Moore SE, Fulford AJ, Prentice AM, Waterland RA. Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Biol. 2015 Jun 11;16(1):118. doi: 10.1186/s13059-015-0660-y.

  PMID: 26062908 RESULT

• Dominguez-Salas P, Moore SE, Cole D, da Costa KA, Cox SE, Dyer RA, Fulford AJ, Innis SM, Waterland RA, Zeisel SH, Prentice AM, Hennig BJ. DNA methylation potential: dietary intake and blood concentrations of one-carbon metabolites and cofactors in rural African women. Am J Clin Nutr. 2013 Jun;97(6):1217-27. doi: 10.3945/ajcn.112.048462. Epub 2013 Apr 10.

  PMID: 23576045 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood, buccal swab, hair follicles

MeSH Terms

Interventions

Seasons; Eating

Intervention Hierarchy (Ancestors)

Periodicity; Time; Physical Phenomena; Climate; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Atmosphere; Meteorological Concepts; Environment and Public Health; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MRC Senior Investigator Scientist

Study Record Dates

• First Submitted: March 11, 2013
• First Posted: March 14, 2013
• Study Start: January 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: December 1, 2015
• Last Updated: March 22, 2016

Record last verified: 2016-03