Abstract
BackgroundIL13, IL4, IL4RA, FCER1B and ADRB2 are 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.Methods989 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.ResultsA four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 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 of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 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 between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2).ConclusionsGene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.
Highlights
The worldwide prevalence of allergic diseases has dramatically increased during the past few decades, resulting in heavy burden to the whole society and huge medical expenditure around the world [1]
Whether the gene–gene interactions among the aforementioned five genes begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) production and cause subsequent allergic diseases have yet to be determined
Selection of genes and single nucleotide polymorphisms This study focused on five candidate genes, including interleukin 13 (IL13), IL4, IL4RA, FCER1B and ADRB2, which are key inflammatory genes affecting IgE levels [10,11,12] and had been found associated with asthma or atopy by more than ten different studies [9]
Summary
The worldwide prevalence of allergic diseases has dramatically increased during the past few decades, resulting in heavy burden to the whole society and huge medical expenditure around the world [1]. The elite group of susceptible genes of asthma and atopy replicated in more than ten different studies include IL13, IL4, IL4RA, FCER1B and ADRB2, five important inflammatory genes associated with IgE levels [10,11,12]. Whether the gene–gene interactions among the aforementioned five genes begin in fetal stage, and whether these genes interact with prenatal environment to enhance CBIgE production and cause subsequent allergic diseases have yet to be determined. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and 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
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