Methyl-Donors and EpiGenetics in The Gambia

Study Overview
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Brief Summary
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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.

Official Title
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Epigenesis in Humans: Can Maternal Methyl-donor-deficient Diets Induce Epigenetic Alterations in Their Offspring?

Conditions
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Aberrant DNA Methylation

Intervention / Treatment
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* Other: season, dietary intake


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| maternal methyl-donors, infant epigenetics<br>women of reproductive age in rural Gambia, infants born to these women | Other: season, dietary intake<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood biomarker status of women | Measurement of blood biomarkers monthly after dietary assessment or in early pregnancy | monthly for 12 months or in early pregnancy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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season of conception, maternal nutritional status, infant DNA methylation