title: Interleukin-4 and interleukin-13 pathway genetics affect disease susceptibility, serum immunoglobulin E levels, and gene expression in asthma.
abstract: BACKGROUND
  Asthma is a common immune disorder characterized by increased IgE levels. The interleukin (IL)-4 and IL-13 pathway is central for IgE regulation, and previous studies have reported many genetic variants of IL-4/IL-13 signaling in relation to asthma, but few have focused on the gene-to-gene interactions that are likely to contribute to disease complexity.
  
  
  OBJECTIVE
  To assess the combined effects of 7 functional single-nucleotide polymorphisms (SNPs) on asthma susceptibility, total serum IgE levels, and gene expression in children.
  
  
  METHODS
  Seven SNPs (rs2243250, rs1800925, rs1805010, rs324011, rs2251746, rs2494262, and rs2427837) were genotyped children with asthma (n = 500) and a control group (n = 523), and total serum IgE levels and gene expressions were measured in children with asthma.
  
  
  RESULTS
  Children with asthma had a likelier possibility of carrying more risk genotypes. Mean IgE levels increased from the minimum of 71.07 KU/L in children with no tested polymorphisms to a maximum of 901.7 KU/L in children carrying 7 risk genotypes. Gene expression analysis showed that patients with 4 SNPs (rs2243250, rs1800925, rs1805010, and rs3224011) had higher expression levels of IL-4, IL-13, and STAT6. Moreover, serum IgE level generally correlated well with IL-4 (r = 0.236, P = .011) and IL-13 (r = 0.211, P = .021) expressions; IL-4 expression correlated positively with IL-13 (r = 0.962, P = .000) and STAT6 (r = 0.190, P = .022) expressions, and STAT6 expression correlated with IL-4RA expression (r = 0.904, P = .000).
  
  
  CONCLUSIONS
  These data suggest that combinations of multiple SNPs might magnify the impact on disease risk. Only a combined analysis of the variants in the IL-4/IL-13 pathway could show the functional interplay of multiple genes in asthma.
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Jia
authors: J
authors: Li
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Li-hui
authors: LH
authors: Lin
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Juan
authors: J
authors: Wang
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Xia
authors: X
authors: Peng
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Hui-rong
authors: HR
authors: Dai
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Hui
authors: H
authors: Xiao
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Fei
authors: F
authors: Li
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Yu-ping
authors: YP
authors: Wang
authors: Shanghai Fosun Med-Tech Development Co, Ltd, Shanghai, China.
authors: Zhi-jun
authors: ZJ
authors: Yang
authors: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: annylish@hotmail.com.
authors: Li
authors: L
authors: Li
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000097:blood* / Q000235:genetics*; D002648:Child; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D018793:Interleukin-13 / Q000097:blood / Q000235:genetics*; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit / Q000097:blood / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050800:STAT6 Transcription Factor / Q000097:blood
chemical_list: C508598:IL4 protein, human; D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4; D007073:Immunoglobulin E