Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children

Rationale: IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene-gene interactions in the five genes among asthmatic children of Chinese Han nationality. Methods: Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor-dimensionality reduction method was applied for the analysis. Results: A four-way gene-gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy=0.6089, cross-validation consistency=10/10, P=6.98E-05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR)=1.24, P=1.23E-03; T allele of rs2243250, OR=1.25, P=3.81E-03; A allele of rs1042713, OR=1.29, P=6.75E-05; G allele of rs569108, OR=1.27, P=3.86E-03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR=13.55, P=4.28E-03), and also greater than those with less than four risk homozygotes (OR=10.09, P=6.51E-03). Conclusions: Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children. Pediatr Pulmonol. 2016;51:364-371. (c) 2015 Wiley Periodicals, Inc.