Department of Pediatrics, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan.
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Clin Exp Allergy. 2019 Aug;49(8):1128-1138. doi: 10.1111/cea.13419. Epub 2019 May 29.
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.
This study aimed to determine whether there are sex-moderated interactions between genetic variants in the IL4/IL13 pathway and prenatal environments on cIgE elevation.
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 STAT6 rs324011).
Gene-environment interactions on cIgE elevation were observed in male but not female newborns, including those between ETS and IL13 rs20541, between home dampness and STAT6 rs324011, and between composite environmental exposure (combined ETS and the three home dampness indices) and STAT6 rs324011 (P for interaction = 0.03, 0.006, and 0.001, respectively). Male newborns carrying STAT6 rs324011 CT or TT genotype manifested with a significant dose-response association of the composite environmental exposure with cIgE elevation.
Sex moderates the gene-environment interactions involving IL4/IL13 pathway genes and prenatal household environments on cIgE elevation. The absence of prenatal exposure to ETS and home dampness in male neonates carrying the STAT6 rs324011 CT or TT genotype is least likely associated with cIgE elevation.
脐带血 IgE（cIgE）升高是特应性疾病的预测因子，受遗传和环境因素的影响。然而，cIgE 升高的基因-环境相互作用及其性别差异在很大程度上仍未得到探索。
本研究旨在确定白细胞介素 4/13（IL4/IL13）通路基因中的遗传变异与产前环境之间是否存在性别调节的相互作用，进而影响 cIgE 升高。
在 1107 例足月新生儿妊娠晚期，使用结构化问卷全面收集环境烟草烟雾（ETS）、家庭潮湿（通过墙壁上的霉味、可见霉菌和水印综合指数来表示）和其他家庭环境等信息。采集脐带血检测 cIgE 水平，cIgE 升高定义为≥0.5IU/mL，并对三个候选基因的五个单核苷酸多态性（IL-13 rs1800925、rs20541、rs848、IL-4 rs2243250 和 STAT6 rs324011）进行基因分型。
cIgE 升高的基因-环境相互作用仅在男性新生儿中观察到，包括 ETS 与 IL13 rs20541、家庭潮湿与 STAT6 rs324011 以及综合环境暴露（ETS 和三个家庭潮湿指数的组合）与 STAT6 rs324011 之间的相互作用（交互作用 P 值分别为 0.03、0.006 和 0.001）。携带 STAT6 rs324011 CT 或 TT 基因型的男性新生儿，复合环境暴露与 cIgE 升高呈显著剂量-反应关系。
性别调节了白细胞介素 4/13 通路基因和产前家庭环境对 cIgE 升高的基因-环境相互作用。携带 STAT6 rs324011 CT 或 TT 基因型的男性新生儿，如果没有接触 ETS 和家庭潮湿，其 cIgE 升高的可能性最小。
