Perinatal Gene-Gene and Gene-Environment Interactions on IgE Production and Asthma Development

Jen-Chieh Chang,Lin Wang,Chieh-An Liu,Rong-Fu Chen

doi:10.1155/2012/270869

Abstract

Atopic asthma is a complex disease associated with IgE-mediated immune reactions. Numerous genome-wide studies identified more than 100 genes in 22 chromosomes associated with atopic asthma, and different genetic backgrounds in different environments could modulate susceptibility to atopic asthma. Current knowledge emphasizes the effect of tobacco smoke on the development of childhood asthma. This suggests that asthma, although heritable, is significantly affected by gene-gene and gene-environment interactions. Evidence has recently shown that molecular mechanism of a complex disease may be limited to not only DNA sequence differences, but also gene-environmental interactions for epigenetic difference. This paper reviews and summarizes how gene-gene and gene-environment interactions affect IgE production and the development of atopic asthma in prenatal and childhood stages. Based on the mechanisms responsible for perinatal gene-environment interactions on IgE production and development of asthma, we formulate several potential strategies to prevent the development of asthma in the perinatal stage.

Highlights

Atopic asthma is a complex disease associated with IgEmediated allergic reactions
We describe recent advances in our understanding based on the mechanisms responsible for gene-gene and geneenvironment interactions on IgE production and development of atopic asthma in the perinatal stage
We conducted a systematic review of recent studies to identify the roles of gene-gene and gene-environmental interactions on the prenatal and childhood IgE production, as well as the development of asthma

Summary

Introduction

Atopic asthma is a complex disease associated with IgEmediated allergic reactions. Most allergens elicit IgE antibodies, which bind to mast cells; when cross-linked, the mast cell releases inflammatory mediators that cause bronchospasm and mucus formation [1]. As with numerous illdefined diseases in which numerous extrinsic influences and genetic factors contribute to onset of the disease, the term “complex disease” is applied. Such terminology refers to asthma as caused by a complex relationship between genetic and environmental components, resulting in the clinical manifestations of atopic asthma. Genetic backgrounds and environmental exposures could modulate susceptibility to asthma [5, 6]. This suggests that asthma, heritable, is significantly affected by environmental factors. CD14-AOAH [13] CD274-LILRA4 [9] GSNOR-B2AR [18] IL4-IL4RA [19] IL6-IL6R [20] IL13-IL4R [21] IL13-IL4RA [15, 17, 22] LTA4H-ALOX5AP [23] SOCS1-MAP3K7IP1 [11] TNC-NPSR1 [24] EPHX1-CYP1B1-CYP2D6 [25] IL2RA-FOXP3-IL2RA [12] IRAK1-NOD1-MAPK7IP1 [11] STAT6-STAT4-IFNG [26] TLR2-IL2RA-TGFBR2 [12] B2AR-CCR3-CysLTR1FCER1B [27] INSIG2-IL4-CHIA-ADIPOQALOX5 [28] IL4-STUB1-ADRB2-IL4RAIL13RA2-CHIA [28]

Gene-Gene Interactions on IgE Production and Asthma Development

Gene-Environment Interactions on IgE Production and Asthma Development

Implications of Gene-Environment Interactions on Prevention of Asthma

Findings

Conclusion