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Genetic variation in the promoter region of chitinase 3-like 1 is associated with atopy.

Authors
 Myung Hyun Sohn  ;  Ji Hyun Lee  ;  Kyung Won Kim  ;  So Won Kim  ;  Sung Hee Lee  ;  Kyu-Earn Kim  ;  Kyung Hwan Kim  ;  Chun Geun Lee  ;  Jack A. Elias  ;  Min Goo Lee 
Citation
 American Journal of Respiratory and Critical Care Medicine, Vol.179(6) : 449-456, 2009 
Journal Title
 American Journal of Respiratory and Critical Care Medicine 
ISSN
 1073-449X 
Issue Date
2009
Abstract
RATIONALE: Atopy or atopic syndrome is an allergic hypersensitivity subject to hereditary influences. Aberrant expression of chitinase 3-like 1 (CHI3L1), also known as YKL-40 or HC gp-39, is involved in the pathogenesis of inflammatory and allergic diseases. OBJECTIVES: The genetic contribution of CHI3L1 gene to atopic susceptibility was investigated using an integrated population genetic and molecular analysis. METHODS: Genetic variations in CHI3L1 were identified and genotyped in 295 unrelated patients with atopy and 180 control subjects. Serum YKL-40 and IgE levels were analyzed according to genotype. The effects of a promoter polymorphism (g.-247C/T) on promoter activity were examined in reporter and protein binding assays. MEASUREMENTS AND MAIN RESULTS: In the case-control association analysis, the g.-247C/T polymorphism at the promoter region (rs10399805; P = 0.0062) and the IVS7+82C/T polymorphism at intron 7 (rs2275353; P = 0.0056) of CHI3L1 showed a significant association with atopy. Subjects with the g.-247T risk allele had significantly higher serum YKL-40 (P < 0.0001) and IgE (P = 0.012) levels. An in vitro promoter assay using THP-1 human monocyte cells revealed that the C to T conversion at g.-247 induced a more than twofold increase of reporter gene expression. Moreover, the g.-247T allele showed an increased affinity for CCAAT enhancer-binding protein, a well known transcriptional activator, by electrophoretic mobility shift assay. Accordingly, subjects with the g.-247TT genotype showed a 2.5-fold increase in CHI3L1 mRNA expression in peripheral blood cells compared with those with the g.-247CC genotype. CONCLUSIONS: These results strongly suggest that the g.-247C/T polymorphism in the CHI3L1 promoter region is associated with the risk of atopy
Full Text
http://www.atsjournals.org/doi/abs/10.1164/rccm.200809-1422OC?journalCode=ajrccm&
DOI
10.1164/rccm.200809-1422OC
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
김경원(Kim, Kyung Won) ORCID logo https://orcid.org/0000-0003-4529-6135
김경환(Kim, Kyung Hwan)
김규언(Kim, Kyu Earn)
김소원(Kim, So Won)
손명현(Sohn, Myung Hyun) ORCID logo https://orcid.org/0000-0002-2478-487X
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
이성희(Lee, Sung Hee)
이지현(Lee, Ji Hyun)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103572
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