Genetic association of acidic mammalian chitinase with atopic asthma and serum total IgE levels

J Allergy Clin Immunol. 2008 Jul;122(1):202-8, 208.e1-7. doi: 10.1016/j.jaci.2008.04.030.

Abstract

Background: In view of the hygiene hypothesis and the involvement of acidic mammalian chitinase (CHIA) in the effector responses of IL-13 with asthma, CHIA (GeneID-27159) is a potential asthma candidate gene.

Objective: To investigate the association of CHIA polymorphisms with atopic asthma and serum total IgE levels.

Methods: Twenty-one single nucleotide polymorphisms were identified by sequencing DNA of 60 individuals. On the basis of linkage disequilibrium, 6 polymorphisms were selected and genotyped in unrelated atopic patients with asthma (N = 270) and controls (N = 292) and an independent pediatric cohort (patients, 150; controls, 101). Electrophoretic mobility shift assay and reporter gene assays were also performed.

Results: The rs3806448G/A promoter polymorphism showed significant association with atopic asthma (P(adult) = .00001 and P(pediatric) = .0002) and serum total IgE (P < .05). Also rs2282290G/A was associated with atopic asthma (P(adult) = .00009 and P(pediatric) = .00003), whereas the rs10494132C/T polymorphism was associated with serum total IgE in the patients (P < .05). We also showed that the promoter single nucleotide polymorphisms altered the transcriptional activity of CHIA promoter and the C to T substitution at rs10494132 abrogated the Octamer transcription factor-1 (Oct-1) binding site.

Conclusion: Our results establish a significant association of CHIA with atopic asthma and serum total IgE levels in the Indian population.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Asthma / enzymology
  • Asthma / genetics*
  • Asthma / immunology
  • Child
  • Chitinases / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Immunoglobulin E / blood*
  • India
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism
  • Male
  • Middle Aged
  • Octamer Transcription Factor-1 / genetics
  • Octamer Transcription Factor-1 / metabolism*
  • Polymorphism, Single Nucleotide*

Substances

  • Interleukin-13
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Immunoglobulin E
  • CHIA protein, human
  • Chitinases