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

Am J Respir Crit Care Med. 2009 Mar 15;179(6):449-56. doi: 10.1164/rccm.200809-1422OC. Epub 2008 Dec 23.


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.

MeSH terms

  • Adipokines
  • CCAAT-Enhancer-Binding Proteins
  • Case-Control Studies
  • Child
  • Chitinase-3-Like Protein 1
  • Electrophoretic Mobility Shift Assay
  • Female
  • Genotype
  • Glycoproteins / blood
  • Glycoproteins / genetics*
  • Humans
  • Hypersensitivity, Immediate / genetics*
  • Immunoglobulin E / blood
  • Korea
  • Lectins
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • RNA, Messenger / metabolism
  • Risk Factors


  • Adipokines
  • CCAAT-Enhancer-Binding Proteins
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Lectins
  • RNA, Messenger
  • Immunoglobulin E