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Polymorphisms and haplotypes of acid mammalian chitinase are associated with bronchial asthma.
American Journal of Respiratory and Critical Care Medicine
Date de publication
Rationale: Chitinases are enzymes that cleave chitin, a polysaccharidecontained in many parasites of humans. Recent studies in mouse modelsof bronchial asthma have shown that acid mammalian chitinase (AMCase)is involved in the pathophysiology of asthma. It acts downstream ofinterleukin-13; inhibition of AMCase leads to an abrogated T-helpercell 2 inflammation, less bronchial hyperreactivity, and fewereosinophils.Objectives: The aim of this study was to identify common geneticvariants in human AMCase and to use them to test for association ofAMCase with pediatric asthma.Methods: By sequencing the promotor region and all 11 exons on 30individuals, 12 high-frequency polymorphisms were identified.Genotyping of six variants in exons and one promotor polymorphism wasperformed on the following populations by means of restriction fragmentlength polymorphisms: 322 children with asthma, 270 randomly chosenadult controls, and a pediatric control population consisting of 565children who, at age 10 yr, had never wheezed and never been diagnosedhaving asthma.Measurements and Main Results: We identified three known and two newamino acid variants. Analyses by the Armitage's trend test using bothcontrol populations showed association of the newly identified variantK17R and the nearby noncoding polymorphism rs3818822 with asthma (p =0.0031 and p = 0.0003, respectively). In addition, haplotype analysesrevealed strong association of haplotypes with the disease (asthmapopulation vs. pediatric control subjects, p < 10(-10)).Conclusions: This newly described association between AMCasepolymorphisms and asthma adds further evidence supporting theinvolvement of AMCase in the development of asthma.
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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