Gene–gene and gene-environment interactions on cord blood total IgE in Chinese Han children

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Abstract
Background: IL13, IL4, IL4RA, FCER1BandADRB2are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population.Methods: 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods.Results: A four-way gene–gene interaction model (IL13rs20541,IL13rs1800925,IL4rs2243250 andADRB2rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805,P = 9.03 × 10–4). Among the four SNPs, onlyIL13rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36,P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers ofIL13rs20541 TT,IL13rs1800925 CT/TT,IL4rs2243250 TT andADRB2rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14,P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found betweenIL4rs2243250 and maternal atopy (OR = 1.41,P = 2.65 × 10–2).Conclusions: Gene–gene interaction betweenIL13rs20541,IL13rs1800925,IL4rs2243250 andADRB2rs1042713, and gene-environment interaction betweenIL4rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.
Funding Information
  • Youth Program of National Nature Science Foundation of China (81900018)
  • the Project for Innovation Teams in Local High Level Universities in Shanghai
  • the Youth Project of Shanghai Municipal Health Commission (20164Y0136)
  • the state key program of national nature science foundation of china (81530086)

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