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.

• Authors: Rajshekhar Chatterjee, Jyotsna Batra, Sudipta Das, Surendra Kumar Sharma, Balaram Ghosh
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 122 Issue 1 Pg. 202-8, 208.e1-7 (Jul 2008) ISSN: 1097-6825 [Electronic] United States
• PMID: 18602573 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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