Association of TGF-beta1, CD14, IL-4, IL-4R and ADAM33 gene polymorphisms with asthma severity in children and adolescents

J Pediatr (Rio J). 2008 May-Jun;84(3):203-10. doi: 10.2223/JPED.1783. Epub 2008 Apr 18.

Abstract

Objective: To verify the association of transforming growth factor-beta1(TGF-beta1) (C-509T and T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) and ADAM33 (S_2) gene polymorphisms with asthma severity in a sample of patients with mild, moderate and severe persistent atopic asthma.

Methods: A clinical, laboratory, prospective study was performed in patients with persistent atopic asthma, compared to a control group at Hospital Universitário da Universidade Estadual de Campinas between 2006 and 2007. Analysis of the TGF-beta1 T869C gene polymorphism was performed using the technique polymerase chain reaction (PCR) + amplification refractory mutation system (ARMS). TGF-beta1 C-509T, CD14 C-159T, IL-4 C-590T, IL-4Ra ILe50Val, and ADAM33 S2 gene polymorphisms were detected by PCR and restriction enzyme.

Results: This study included 88 patients with persistent atopic asthma (27 mild, 23 moderate and 38 severe) and 202 healthy blood donors. As to T869C polymorphism (TGF-beta1), there was an association between the CC genotype and patients with severe asthma. There was no association in polymorphisms C-509T (TGF-beta1), C-590T (IL-4) and S_2 (ADAM33). When distribution of C-159T polymorphism genotype frequency (CD14) in severe asthma was compared with the control group, there was a significant result with the TT genotype. There was significant association of the Val/Val genotype (IL-4R) with mild asthma.

Conclusion: Our results indicate that T869C (TGF-beta1), C-159T (CD14) and Val/Val (IL-4R) polymorphisms might be involved in modulation of asthma severity.

MeSH terms

  • ADAM Proteins / genetics*
  • Adolescent
  • Asthma / genetics*
  • Case-Control Studies
  • Child
  • Cytokines / genetics*
  • Female
  • Genetic Markers / genetics
  • Genotype
  • Humans
  • Interleukin-4 / genetics
  • Lipopolysaccharide Receptors / genetics
  • Male
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Prospective Studies
  • Receptors, Immunologic / genetics*
  • Receptors, Interleukin-4 / genetics
  • Severity of Illness Index
  • Transforming Growth Factor beta1 / genetics

Substances

  • Cytokines
  • Genetic Markers
  • Lipopolysaccharide Receptors
  • Receptors, Immunologic
  • Receptors, Interleukin-4
  • Transforming Growth Factor beta1
  • Interleukin-4
  • ADAM Proteins
  • ADAM33 protein, human