title: Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hua
authors.affiliation: Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, Anhui, China.
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi-Xiao
authors.initials: YX
authors.lastname: Bao
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Quan-Hua
authors.initials: QH
authors.lastname: Liu
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing-Yang
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ding-Zhu
authors.initials: DZ
authors.lastname: Fang
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ruo-Xu
authors.initials: RX
authors.lastname: Ji
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000208:ethnology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D017455:Receptors, IgE / Q000235:genetics*
chemical_list: C553443:ADRB2 protein, human; C578095:IL13 protein, human; C508598:IL4 protein, human; D018793:Interleukin-13; C502447:MS4A2 protein, human; D018343:Receptors, Adrenergic, beta-2; D017455:Receptors, IgE; D015847:Interleukin-4
keywords: IL13; asthma; gene-gene interactions; multifactor-dimensionality reduction; single-nucleotide polymorphism