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Four‐locus gene interaction between IL13 , IL4 , FCER1B , and ADRB2 for asthma in Chinese Han children
Author(s) -
Hua Li,
Zuo XianBo,
Bao YiXiao,
Liu QuanHua,
Li JingYang,
Lv Jie,
Fang DingZhu,
Lin Qian,
Bao Jun,
Ji RuoXu
Publication year - 2016
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.23322
Subject(s) - single nucleotide polymorphism , asthma , allele , medicine , odds ratio , interleukin 13 , multifactor dimensionality reduction , genetics , interleukin 4 , genotype , gene , immunology , biology , cytokine
Summary 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 . © 2015 Wiley Periodicals, Inc.