Genetic Variation in the Promoter Region of Chitinase 3-Like 1 Is Associated with Atopy

• DOI: 10.1164/rccm.200809-1422oc
• Publication Date: 2008-12-24T02:49:08Z
• 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
• Keywords: Atopy; Pathogenesis

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 HC gp-39, involved in the pathogenesis inflammatory and diseases.The genetic contribution CHI3L1 gene susceptibility was investigated using integrated population molecular analysis.Genetic variations were identified genotyped 295 unrelated patients with atopy 180 control subjects. Serum IgE levels analyzed according genotype. The effects a promoter polymorphism (g.-247C/T) on activity examined reporter protein binding assays.In case-control association analysis, g.-247C/T at region (rs10399805; P = 0.0062) IVS7+82C/T intron 7 (rs2275353; 0.0056) showed significant atopy. Subjects g.-247T risk allele had significantly higher serum (P < 0.0001) 0.012) levels. An vitro assay THP-1 human monocyte cells revealed that C T conversion g.-247 induced more than twofold increase expression. Moreover, increased affinity for CCAAT enhancer-binding protein, well transcriptional activator, by electrophoretic mobility shift assay. Accordingly, subjects g.-247TT genotype 2.5-fold mRNA peripheral blood compared those g.-247CC genotype.These results strongly suggest associated