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Proc Natl Acad Sci U S A. 2017 Jul 18;114(29):7611-7616. doi: 10.1073/pnas.1620661114. Epub 2017 Jul 3.

Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood.

Author information

1
Department of Anthropology, Northwestern University, Evanston, IL 60208; t-mcdade@northwestern.edu.
2
Institute for Policy Research, Northwestern University, Evanston, IL 60208.
3
Child and Brain Development Program, Canadian Institute for Advanced Research, Toronto, Ontario M5G 1Z8, Canada.
4
Department of Anthropology, Northwestern University, Evanston, IL 60208.
5
BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
6
Department of Sociology, Northwestern University, Evanston, IL 60208.
7
USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines.
8
Department of Nutrition and Dietetics, University of San Carlos, Cebu City, Philippines.
9
Department of Psychology, Northwestern University, Evanston, IL 60208.

Abstract

Chronic inflammation contributes to a wide range of human diseases, and environments in infancy and childhood are important determinants of inflammatory phenotypes. The underlying biological mechanisms connecting early environments with the regulation of inflammation in adulthood are not known, but epigenetic processes are plausible candidates. We tested the hypothesis that patterns of DNA methylation (DNAm) in inflammatory genes in young adulthood would be predicted by early life nutritional, microbial, and psychosocial exposures previously associated with levels of inflammation. Data come from a population-based longitudinal birth cohort study in metropolitan Cebu, the Philippines, and DNAm was characterized in whole blood samples from 494 participants (age 20-22 y). Analyses focused on probes in 114 target genes involved in the regulation of inflammation, and we identified 10 sites across nine genes where the level of DNAm was significantly predicted by the following variables: household socioeconomic status in childhood, extended absence of a parent in childhood, exposure to animal feces in infancy, birth in the dry season, or duration of exclusive breastfeeding. To evaluate the biological significance of these sites, we tested for associations with a panel of inflammatory biomarkers measured in plasma obtained at the same age as DNAm assessment. Three sites predicted elevated inflammation, and one site predicted lower inflammation, consistent with the interpretation that levels of DNAm at these sites are functionally relevant. This pattern of results points toward DNAm as a potentially important biological mechanism through which developmental environments shape inflammatory phenotypes across the life course.

KEYWORDS:

developmental origins of disease; developmental origins of health; ecological immunology; epigenetics; inflammation

PMID:
28673994
PMCID:
PMC5530653
DOI:
10.1073/pnas.1620661114
[Indexed for MEDLINE]
Free PMC Article

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