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

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 case–control children and its functional relevance was investigated. Methods. Genotyping of a non-coding variant G+38A 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 G+38A 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 G+38A variant may contribute to the severity of asthma and lower level of steroid responsiveness.

• acute exacerbation
• asthma
• CC10
• gene polymorphism
• uteroglobin

Acknowledgments

We thank Ms. Shih-Ting Tsao and Ms. Ai-Hsuan Wu for excellent technical assistance. This work was supported, in part, by National Science Council (NSC95-2314-B-182A-169), National Health Research Institute (NHRI-EX96-9629SI), Chang Gung Memorial Hospital (CMRPG 260281), Taiwan, and NIH grants (AI-052468 and AI-073610), USA. This work was also supported, in part, by grants from National Health Research Institute, Taiwan (#EOPP10-014 and #EOSP07-014) and Ministry of Health, Taiwan (#EODOH01).

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.