Genetic association of acidic mammalian chitinase with atopic asthma and serum total IgE levels.
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.
Chatterjee
Rajshekhar
R
Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi, India.
Batra
Jyotsna
J
Das
Sudipta
S
Sharma
Surendra Kumar
SK
Ghosh
Balaram
B
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
D018793:Interleukin-13; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D007073:Immunoglobulin E; C499254:CHIA protein, human; D002688:Chitinases