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Sex‐moderated interactions between IL 4/ IL 13 pathway genes and prenatal environment on cord blood IgE levels
Author(s) -
Chen ChienHan,
Lee Yungling Leo,
Wu MingHsun,
Chen PaoJen,
Wei TienShan,
Chen PauChung,
Tseng ChingIng,
Chen Wei J.
Publication year - 2019
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13419
Subject(s) - cord blood , pregnancy , single nucleotide polymorphism , genotype , medicine , tobacco smoke , immunology , gene , genotyping , andrology , physiology , biology , genetics , environmental health
Abstract Background Elevated cord blood IgE ( cIgE ), a predictor of atopic diseases, is influenced by genetic and environmental factors. However, gene‐environment interactions on cIgE elevation and their difference by sex remain largely unexplored. Objective This study aimed to determine whether there are sex‐moderated interactions between genetic variants in the IL 4/ IL 13 pathway and prenatal environments on cIgE elevation. Methods Comprehensive information on environmental tobacco smoke ( ETS ), home dampness (indexed by combining mildewy odour, visible mould and water stamp on the wall) and other household environments was obtained using a structured questionnaire during the third trimester of pregnancy in 1107 full‐term newborns. The cord blood was collected for measuring cIgE levels, with elevation defined as ≥0.5 IU / mL , and for genotyping of five single nucleotide polymorphisms of three candidate genes ( IL ‐13 rs1800925, rs20541, rs848, IL ‐4 rs2243250 and STAT 6 rs324011). Results Gene‐environment interactions on cIgE elevation were observed in male but not female newborns, including those between ETS and IL 13 rs20541, between home dampness and STAT 6 rs324011, and between composite environmental exposure (combined ETS and the three home dampness indices) and STAT 6 rs324011 ( P for interaction = 0.03, 0.006, and 0.001, respectively). Male newborns carrying STAT 6 rs324011 CT or TT genotype manifested with a significant dose‐response association of the composite environmental exposure with cIgE elevation. Conclusion and Clinical Relevance Sex moderates the gene‐environment interactions involving IL 4/ IL 13 pathway genes and prenatal household environments on cIgE elevation. The absence of prenatal exposure to ETS and home dampness in male neonates carrying the STAT 6 rs324011 CT or TT genotype is least likely associated with cIgE elevation.