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

Abstract

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