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