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Polymorphisms and haplotypes of acid mammalian chitinase are associated with bronchial asthma.

AbstractRATIONALE:
Chitinases are enzymes that cleave chitin, a polysaccharide contained in many parasites of humans. Recent studies in mouse models of bronchial asthma have shown that acid mammalian chitinase (AMCase) is involved in the pathophysiology of asthma. It acts downstream of interleukin-13; inhibition of AMCase leads to an abrogated T-helper cell 2 inflammation, less bronchial hyperreactivity, and fewer eosinophils.
OBJECTIVES:
The aim of this study was to identify common genetic variants in human AMCase and to use them to test for association of AMCase with pediatric asthma.
METHODS:
By sequencing the promotor region and all 11 exons on 30 individuals, 12 high-frequency polymorphisms were identified. Genotyping of six variants in exons and one promotor polymorphism was performed on the following populations by means of restriction fragment length polymorphisms: 322 children with asthma, 270 randomly chosen adult controls, and a pediatric control population consisting of 565 children who, at age 10 yr, had never wheezed and never been diagnosed having asthma.
MEASUREMENTS AND MAIN RESULTS:
We identified three known and two new amino acid variants. Analyses by the Armitage's trend test using both control populations showed association of the newly identified variant K17R and the nearby noncoding polymorphism rs3818822 with asthma (p = 0.0031 and p = 0.0003, respectively). In addition, haplotype analyses revealed strong association of haplotypes with the disease (asthma population vs. pediatric control subjects, p < 10(-10)).
CONCLUSIONS:
This newly described association between AMCase polymorphisms and asthma adds further evidence supporting the involvement of AMCase in the development of asthma.
AuthorsSibylle Bierbaum, Renate Nickel, Anja Koch, Susanne Lau, Klaus A Deichmann, Ulrich Wahn, Andrea Superti-Furga, Andrea Heinzmann
JournalAmerican journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 172 Issue 12 Pg. 1505-9 (Dec 15 2005) ISSN: 1073-449X [Print] United States
PMID16179638 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • CHIA protein, human
  • Chitinase
Topics
  • Adolescent
  • Adult
  • Asthma (genetics)
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Chitinase (genetics)
  • Exons (genetics)
  • Female
  • Haplotypes (genetics)
  • Humans
  • Male
  • Polymorphism, Genetic (genetics)
  • Promoter Regions, Genetic (genetics)

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