title: Interleukin-4 (IL4) and Interleukin-4 receptor (IL4RA) polymorphisms in asthma: a case control study.
abstract: BACKGROUND
  IL4/IL4RA pathway plays an important role in atopy and asthma. Different polymorphisms in IL4 and IL4RA genes have been described. Particularly, -33C>TIL4 and 576Q>RIL4RA SNPs have been independently associated to atopy and asthma. The purpose of this study was to analyse these polymorphisms in a population of patients with a well-characterized asthma phenotype.
  
  
  METHODS
  A total of 212 unrelated Caucasian individuals, 133 patients with asthma and 79 healthy subjects without symptoms or history of asthma or atopy and with negative skin prick tests were recruited. Lung function was measured by spirometry and asthma was specialist physician-diagnosed according to the ATS (American Thoracic Society) criteria and classified following the GINA (Global Initiative for Asthma) guidelines. Skin prick tests were performed according to EAACI recommendations. -33C>TIL4 was studied with TaqMan assay and 576Q>RIL4RA by PCR-RFLP technique. Hardy-Weinberg equilibrium was analysed in all groups. Dichotomous variables were analysed using chi2, Fisher exact test, Monte Carlo simulation test and odds ratio test. To model the effects of multiple covariates logistic regression was used.
  
  
  RESULTS
  No statistically significant differences between the group of patients with asthma and the controls were found when the allele and genotype distribution of -33C>TIL4 and 576Q>RIL4RA polymorphisms were compared. However, the T allele of the -33C>TIL4 SNP was more frequent in patients with persistent asthma. Multivariate analysis adjusted for age and sex confirmed that carriers of allele T had an increased risk of persistent asthma (OR: 2.77, 95%CI: 1.18-6.49; p = 0.019). Analysis of combination of polymorphisms showed that patients carrying both the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA had an increased risk of asthma. This association was particularly observed in persistent asthma [Fisher's p value = 0.0021, Monte Carlo p value (after 10(4) simulations) = 0.0016, OR:3.39; 95% CI:1.50-7.66].
  
  
  CONCLUSIONS
  Our results show a trend of association between the genetic combination of the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA with asthma. This genetic variant was more frequently observed in patients with persistent asthma. As long as this study was performed in a small population, further studies in other populations are needed to confirm these results.
authors.affiliation: Molecular Medicine Unit, Department of Medicine, Faculty of Medicine, University of Salamanca, Campus Miguel de Unamuno, Salamanca 37008, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Isidoro-García
authors.affiliation: Department of Allergy, University Hospital of Salamanca, Paseo de San Vicente 58, Salamanca 37007, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Dávila
authors.affiliation: Department of Allergy, University Hospital of Salamanca, Paseo de San Vicente 58, Salamanca 37007, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Laffond
authors.affiliation: Department of Allergy, University Hospital of Salamanca, Paseo de San Vicente 58, Salamanca 37007, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Moreno
authors.affiliation: Department of Allergy, University Hospital of Salamanca, Paseo de San Vicente 58, Salamanca 37007, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Lorente
authors.affiliation: Molecular Medicine Unit, Department of Medicine, Faculty of Medicine, University of Salamanca, Campus Miguel de Unamuno, Salamanca 37008, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento