title: Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population.
abstract: BACKGROUND
  IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype.
  
  
  OBJECTIVE
  To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Ralpha chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma.
  
  
  METHODS
  Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Ralpha chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England.
  
  
  RESULTS
  Case-control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006).
  
  
  CONCLUSIONS
  Our data suggest that polymorphisms in the IL-4 and IL-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.
authors.affiliation: Divisions of Human Genetics Infection, Inflammation and Repair, School of Medicine, University of Southampton, UK. bianca.beghe@unipd.it
authors.forename: B
authors.initials: B
authors.lastname: Beghé
authors.forename: S
authors.initials: S
authors.lastname: Barton
authors.forename: S
authors.initials: S
authors.lastname: Rorke
authors.forename: Q
authors.initials: Q
authors.lastname: Peng
authors.forename: I
authors.initials: I
authors.lastname: Sayers
authors.forename: T
authors.initials: T
authors.lastname: Gaunt
authors.forename: T P
authors.initials: TP
authors.lastname: Keith
authors.forename: J B
authors.initials: JB
authors.lastname: Clough
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: J W
authors.initials: JW
authors.lastname: Holloway
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: D019948:Receptors, Interleukin-4; D015847:Interleukin-4