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Early life precursors, epigenetics, and the development of food allergy

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Abstract

Food allergy (FA), a major clinical and public health concern worldwide, is caused by a complex interplay of environmental exposures, genetic variants, gene–environment interactions, and epigenetic alterations. This review summarizes recent advances surrounding these key factors, with a particular focus on the potential role of epigenetics in the development of FA. Epidemiologic studies have reported a number of nongenetic factors that may influence the risk of FA, such as timing of food introduction and feeding pattern, diet/nutrition, exposure to environmental tobacco smoking, prematurity and low birth weight, microbial exposure, and race/ethnicity. Current studies on the genetics of FA are mainly conducted using candidate gene approaches, which have linked more than 10 genes to the genetic susceptibility of FA. Studies on gene–environment interactions of FA are very limited. Epigenetic alteration has been proposed as one of the mechanisms to mediate the influence of early life environmental exposures and gene–environment interactions on the development of diseases later in life. The role of epigenetics in the regulation of the immune system and the epigenetic effects of some FA-associated environmental exposures are discussed in this review. There is a particular lack of large-scale prospective birth cohort studies that simultaneously assess the interrelationships of early life exposures, genetic susceptibility, epigenomic alterations, and the development of FA. The identification of these key factors and their independent and joint contributions to FA will allow us to gain important insight into the biological mechanisms by which environmental exposures and genetic susceptibility affect the risk of FA and will provide essential information to develop more effective new paradigms in the diagnosis, prevention, and management of FA.

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Abbreviations

ACSL:

Actyl-CoA synthetase long-chain family, member 3

AIMs:

Ancestry informative markers

BBC:

Boston Birth Cohort

CTLA4:

Cytotoxic T lymphocyte-associated protein 4

CYP24A1:

Cytochrome P450, family 24, subfamily A, polypeptide 1

DCs:

Dendritic cells

DNMT:

DNA methyltransferase

ETS:

Environmental tobacco smoke

FA:

Food allergy

FCER1G:

Fc fragment of IgE, high affinity I, receptor for gamma polypeptide

FLG:

Filaggrin

FOXP3:

Forkhead box P3

FS:

Food sensitization

GSTP1:

Glutathione S-transferase pi 1

GWA:

Genome-wide association

HDACs:

Histone deacetylase

IFNG:

Interferon, gamma

IgE:

Immunoglobulin E

IL:

Interleukin

IL12RB1:

IL12 receptor, beta 1

IL4RA:

IL4 receptor alpha

LBW:

Low birth weight

MS4A2:

Membrane-spanning 4-domains, subfamily A, member 2

NHANES:

National Health and Nutrition Examination Survey

NLRP3:

NLR family, pyrin domain containing 3

PGE2:

Prostaglandin E2

PTPRO:

Protein tyrosine phosphatase receptor type O

LC-PUFAs:

Long-chain polyunsaturated fatty acids

SPINK5:

Serine peptidase inhibitor, Kazal type 5

STAT6:

Signal transducer and activator of transcription 6

TNFα:

Tumor necrosis factor, alpha

T reg:

T regulatory

TSLP:

Thymic stromal lymphopoietin

TLR:

Toll-like receptor

VDD:

Vitamin D deficiency

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Acknowledgments

Drs. Wang and Hong have been supported in part by the Food Allergy Initiative, the National Institute of Allergy and Infectious Diseases (PI: Wang, R21AI079872, R21AI088609, U01AI090727), and the Department of Defense (PI: Wang, W81XWH-10-1-0123). We thank Tami Bartell for the English editing.

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  1. Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, E4005, Baltimore, MD, 21205-2179, USA

    Xiumei Hong

  2. Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, E4132, Baltimore, MD, 21205-2179, USA

    Xiaobin Wang

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Correspondence to Xiaobin Wang.

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This article is published as part of the Special Issue on Food Allergy [34:6].

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Hong, X., Wang, X. Early life precursors, epigenetics, and the development of food allergy. Semin Immunopathol 34, 655–669 (2012). https://doi.org/10.1007/s00281-012-0323-y

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