摘要
目的：编码Clara细胞10-kDa蛋白（CC10）的基因（SCGB1A1）是一个激素诱导性免疫调节因子，是哮喘的一个候选基因，但临床证据存在分歧。本试验为一项病例对照研究，在中国患儿中研究该基因的一个常见变异体对哮喘严重程度和哮喘急性加重和激素治疗后血清CC10的影响。
方法：在489名儿童中，对非编码的G+38A进行基因分型。其中277名儿童患有不同程度的哮喘，212名健康对照。评价哮喘、哮喘严重程度和激素治疗反应性之间的关系。在Clara样细胞株（H358）中采用瞬时转染分析，评价该变异体的转录活性。
结果：CC10 G+38A变异体的GA和AA基因型两者与哮喘风险增加显著相关（OR 2.62, P<0.001）。该相关性与哮喘严重程度相关（中度哮喘：OR, 2.85, P<0.001；近乎致命性哮喘：OR, 4.81, P<0.001）。与GG基因型患者相比，GA和AA基因型的患者血清CC10更低（P< 0.01），导致第一秒用力呼气体积（FEV 1）下降20%的激发物浓度更低（P< 0.0001）。激素治疗后，GG基因型哮喘患者的CC10水平显著增加（P<0.0001），但GA和AA基因型患者CC10无显著变化。此外， 与野生型等位基因（G）相比，瞬时转染G38A风险等位基因（A）的H358细胞，地塞米松诱导的报告基因（萤光素酶）活性更低。
结论：研究结果显示，CC10 G+38A变异体与中国哮喘患儿的哮喘严重程度和激素治疗低反应性有关。
（林江涛 审校）
J Asthma. 2012 Jul 13. [Epub ahead of print]
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.
Chen LC, Tseng HM, Wu CJ, Kuo ML, Wu CJ, Gao PS, Yeh KW, Yao TC, Lee WI, Ou LS, Huang JL, Huang SK.
Source
The Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University , Taoyuan , Taiwan.
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 (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.
J Asthma. 2012 Jul 13. [Epub ahead of print]
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