Methyl-Donors and EpiGenetics in The Gambia

NCT ID: NCT01811641

Last Updated: 2016-03-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 166 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2015-12-31

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

maternal methyl-donors, infant epigenetics

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

season, dietary intake

Intervention Type: OTHER

Interventions

season, dietary intake

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• born to the above women

Exclusion Criteria

• 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

• those known to be severely malnourished (weight-for-height Z-score < -3)

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: lead

Responsible Party

Matt Silver

MRC Senior Investigator Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

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.

Reference Type: RESULT

PMID: 24781383 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26062908 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23576045 (View on PubMed)

Other Identifiers

MRC-ING-MDEG

Identifier Type: -

Identifier Source: org_study_id