Clinical trial NCT01811641: Methyl-Donors and EpiGenetics in The Gambia
Official title: Epigenesis in Humans: Can Maternal Methyl-donor-deficient Diets Induce Epigenetic Alterations in Their Offspring?
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aberrant DNA Methylation
Keywords: season of conception
maternal nutritional status
infant DNA methylation
Lead sponsor: Medical Research Council
Sponsor class: OTHER_GOV
First posted: 2013-03-14
Enrollment: 166
Sex: ALL
Minimum age (years): 1
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: women of reproductive age in rural Gambia and their infants

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.


Eligibility criteria: Inclusion criteria women:

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

Exclusion criteria women:

* 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

Inclusion criteria infants:

- born to the above women

Exclusion criteria infants:

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

Primary outcomes:
measure: DNA methylation of infants
timeFrame: infants: at 3-6 months of age
Secondary outcomes:
measure: Blood biomarker status of women
timeFrame: monthly for 12 months or in early pregnancy
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.