CC16 A38G 基因多型性和過敏性鼻炎併發氣喘相關性之研究

The association between CC16 A38G polymorphism and the development of asthma in children with allergic rhinitis

顧明修(Min-Sho Ku)

指導教授 ： 呂克桓 ； 楊順發

中山醫學大學/醫學院/醫學研究所/博士(2013年)

https://doi.org/10.6834/CSMU.2013.00024

摘要

背景:
雖然氣喘及過敏病性鼻炎，被認為是同一呼吸道過敏疾病，在不同位置的表現，但是至今氣喘及過敏性鼻炎間，有許多未被了解的問題。為什麼有些過敏性鼻炎的患者日後會出現氣喘？而其他人不會?至今仍然沒有明確答案。
目標:
我們假設，過敏性鼻炎兒童中，有Clara細胞分泌蛋白(CC16, secretoglobin 1A1)基因A38G多型性中，38A/38A基因型的人，日後出現氣喘的機率會比較高。
方法:
本研究的對照組包含217名兒童，他們有過敏性鼻炎，但在過敏性鼻炎診斷後5年沒有氣喘的併發。本研究的實驗組包含202名兒童。他們的年紀和性別比例和對照組相似。這些實驗組兒童先有過敏性鼻炎，在過敏性鼻炎診斷後3-5年間出現氣喘。CC16基因A38G多型性的基因型，由聚合酵素連鎖反應 (polymerase chain reaction, PCR)，利用 “Sau96 I” 限制酶切聚合酶反應產物來取得。血清CC16蛋白濃度由酵素連結免疫吸附分析法(Enzyme-Linked Immunosorbent Assay, ELISA)得知。此外兩組兒童之血液嗜酸性求(eosinophil)數，血清IgE總值(serum total IgE)，過敏原特異性IgE (allergen specific IgE)，肺功能亦加以檢測。
結果:
在實驗組(過敏性鼻炎日後併發氣喘)兒童中，擁有CC16基因A38G多型性的AA基因型比例，比對照組(過敏性鼻炎日後沒有併發氣喘)的兒童高。[odds ratio (OR) = 2.527; 95% confidence interval (CI) = 1.571–4.065; P < 0.01]。在實驗組兒童中，擁有AA基因型的人其血清CC16濃度，比實驗組中擁有非AA基因型的人低。實驗組兒童，擁有AA基因型的人其血清CC16濃度，也比所有對照組兒童的低。
結論及臨床應用:
我們的研究結果顯示，CC16基因A38G多型性的38A/38A基因型，在過敏性鼻炎併發氣喘的過程中，扮演一定的角色。早期發現哪些過敏性鼻炎兒童有較高的機率在日後會併發氣喘，有助於盡早採取預防措施，避免這些兒童日後出現氣喘。

關鍵字

過敏性鼻炎 ； 氣喘 ； 過敏體質 ； CC10 ； CC16 ； CCSP ； 兒童 ； 基因多型性 ； secretoglobin 1 A1 ； uteroglobin

並列摘要

Background:
Although asthma and allergic rhinitis (AR) are considered to be one syndrome, many questions remain unanswered. Why do some AR patients develop asthma but others do not, and which factors play a role in the development of asthma that have so far not been clearly elucidated.
Objective:
We hypothesize that children with AR who have the Clara cell secretory protein (CC16, secretoglobin 1A1) 38A/38A genotype have an increased likelihood of developing asthma.
Methods:
The study sample included 217 children, with AR, but no asthma diagnosed within the following 5 years, as the control group. Cases group (n = 202) included age- and gendermatched children with AR first, and asthma developed 3–5 years later, as the study group. The CC16 genotype was determined by PCR and Sau96I restriction digestion of PCR products. The serum CC16 levels were measured by ELISA. Total serum IgE, allergen specific IgE, eosinophil count and pulmonary function were also measured.
Results:
In children with rhinitis who develop asthma, the frequencies of the AA genotype were significantly higher than those who did not develop asthma [odds ratio (OR) = 2.527; 95% confidence interval (CI) = 1.571–4.065; P < 0.01]. Serum CC16 levels in the children with rhinitis who develop asthma and carry the AA genotype were significantly lower than those who carry the non-AA genotype and those who did not develop asthma.
Conclusions and Clinical Relevance:
Results of this study suggest that CC16 38A/38A genotype plays a role in the development of early asthma in children with AR. Early identification of rhinitis children at risk may assist in designing preventative approach to asthma development.

並列關鍵字

allergic rhinitis ； asthma ； atopy ； CC10 ； CC16 ； CCSP ； childhood ； polymorphism ； secretoglobin 1 A1 ； uteroglobin

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