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.
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 (PC(20)) in forced expiratory volume in 1 s (FEV(1)) (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.
The Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Li-Chen
LC
Chen
Hsu-Min
HM
Tseng
Chia-Jen
CJ
Wu
Ming-Ling
ML
Kuo
Cheng-Jang
CJ
Wu
Pei-Song
PS
Gao
Kuo-Wei
KW
Yeh
Tsung-Chieh
TC
Yao
Wen-I
WI
Lee
Liang-Shiou
LS
Ou
Jing-Long
JL
Huang
Shau-Ku
SK
Huang
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014598:Uteroglobin / Q000097:blood / Q000235:genetics*
D000305:Adrenal Cortex Hormones; C556389:SCGB1A1 protein, human; D014598:Uteroglobin