Evaluation of a common variant of the gene encoding clara Cell 10 kd Protein (CC10) as a candidate determinant for asthma severity and steroid responsiveness among chinese children

Li Chen Chen, Hsu Min Tseng, Chia Jen Wu, Ming Ling Kuo, Cheng Jang Wu, Pei Song Gao, Kuo Wei Yeh, Tsung Chieh Yao, Wen I. Lee, Liang Shiou Ou, Jing Long Huang, Shau Ku Huang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective. The gene (SCGB1A1) encoding Clara cell 10-kDa protein (CC10), a steroid-inducible immune modulator, is a candidate gene for asthma, but the evidence is equivocal. The potential influence of a common variant on asthma severity and serum CC10 levels during acute exacerbation and after corticosteroid treatment in Chinese casecontrol children and its functional relevance was investigated. Methods. Genotyping of a non-coding variant G38A was performed in 489 children, of whom 277 had asthma with varying severity, and 212 healthy controls. Associations were tested for asthma, asthma severity, and responsiveness to steroid treatment. The transcriptional activity of this variant was examined in a Clara-like cell line (H358) using transient transfection assays. Results. Significant association was observed for the combined GA and AA genotypes of the CC10 G38A variant and an increased risk of asthma [odds ratio (OR), 2.62, p < .001]. This association was correlated with asthma severity (moderate: OR, 2.85, p < .001; near-fatal: OR, 4.81, p < .001). Also, patients with the GA and AA genotypes showed significantly lower serum CC10 (p < .01) and provocation concentration causing a 20 fall (PC20) in forced expiratory volume in 1 s (FEV1) (p < .0001) when compared with those with the GG. After glucocorticoid treatment, the CC10 levels were significantly increased in asthmatic patients with GG (p < .0001), but not those with the GA and AA genotypes. Moreover, a lower dexamethasone-induced reporter (luciferase) activity was observed for H358 cells transiently transfected with the G38A risk allele (A) compared with wild-type allele (G). Conclusions. These findings suggest that the CC10 G38A variant may contribute to the severity of asthma and lower level of steroid responsiveness.

Original languageEnglish
Pages (from-to)665-672
Number of pages8
JournalJournal of Asthma
Volume49
Issue number7
DOIs
Publication statusPublished - Sep 1 2012
Externally publishedYes

Keywords

  • Acute exacerbation
  • Asthma
  • CC10
  • Gene polymorphism
  • Uteroglobin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Immunology and Allergy
  • Pulmonary and Respiratory Medicine

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