Environmental tobacco smoke and male sex modify the influence of IL-13 genetic variants on cord blood IgE levels

To cite this article: Chen C‐H, Lee YL, Wu M‐H, Chen P‐J, Wei T‐S, Wu C‐T, Tung K‐Y, Chen WJ. Environmental tobacco smoke and male sex modify the influence of IL‐13 genetic variants on cord blood IgE levels. Pediatric Allergy Immunology 2012: 23: 456–463. Elevated cord blood IgE (cIgE) levels enhance the risk of childhood atopic diseases. However, genetic determinants of cIgE elevation and their potential modifiers remain inconclusive. We aimed to investigate the associations of single‐nucleotide polymorphisms (SNPs) in the IL‐13 gene (IL‐13) with cIgE elevation and their interactions with prenatal environmental tobacco smoke (ETS) and neonatal sex. A structured questionnaire regarding prenatal environmental exposures was completed during pregnancy. Birth information was extracted from the medical records. Cord blood from 794 term neonates was genotyped for three SNPs (rs1800925, rs20541, and rs848) of IL‐13 and measured for cIgE levels. SNP rs20541 and a 3‐SNP haplotype containing rs1800925, rs20541, and rs848 (denoted as h011) were significantly associated with cIgE elevation (p = 0.04 and 0.003, respectively). Two‐way interaction analysis revealed that the associations of IL‐13 rs20541 and h011 with cIgE elevation were synergistically enhanced by prenatal ETS (p for interaction = 0.03 and 0.03, respectively), but not by male sex. If the association analyses were stratified by prenatal ETS and neonatal sex simultaneously, IL‐13 rs20541 and h011 had the highest risks for cIgE elevation in male babies prenatally exposed to ETS, with adjusted odds ratios (95% confidence interval) being 3.03 (1.56–5.88) and 2.81 (1.54–5.15), respectively. When three‐way interactions were examined, both IL‐13 rs20541 and h011 exhibited significant interactions with male sex and ETS (p for interaction = 0.03 and 0.007, respectively). In conclusion, the influence of IL‐13 genetic variants on cIgE elevation was modified by male sex and prenatal ETS.