title: Genetic association of acidic mammalian chitinase with atopic asthma and serum total IgE levels.
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.
  
  
  CONCLUSIONS
  Our results establish a significant association of CHIA with atopic asthma and serum total IgE levels in the Indian population.
authors.affiliation: Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Rajshekhar
authors.initials: R
authors.lastname: Chatterjee
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Batra
authors.forename: Sudipta
authors.initials: S
authors.lastname: Das
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001249:Asthma / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D002648:Child; D002688:Chitinases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007194:India; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: D018793:Interleukin-13; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D007073:Immunoglobulin E; C499254:CHIA protein, human; D002688:Chitinases