CD14, STAT6及人類E-cadherin基因多形性在兒童氣喘之易感受性角色

中山醫學大學機構典藏 CSMUIR > 健康管理學院 > 公共衛生學系暨碩士班 > 研究計劃 > Item 310902500/3036

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/3036

Title:	CD14, STAT6及人類E-cadherin基因多形性在兒童氣喘之易感受性角色 The Susceptible Role of CD14, STAT6, and Human E-Cadherin Genetic Polymorphisms in Childhood Asthma
Authors:	翁瑞宏;呂克桓 Wong, Ruey-Hong
Contributors:	中山醫學院公共衛生系
Keywords:	CD14基因;STAT6基因;CDH1基因;兒童氣喘;過敏原 CD14 gene;STAT6 gene;CDH1 gene;childhood asthma;Allergen
Date:	2006
Issue Date:	2010-12-06T03:23:43Z (UTC)
Abstract:	第二型輔助T 淋巴球 (Th2 細胞) 和其他細胞激素在氣喘的致病過程中扮演著重要的角色。CD14 為細菌細胞壁成分的多功能接受器，並可能調節兒童時期早期Th1-Th2 的比例。信號轉導和轉錄啟動因子(signal transducer and activator transcription [Stat]) 6 則為影響Th2 細胞分化的重要轉錄因子。香菸暴露對於兒童氣喘發生的致病機轉，至今仍不清楚。並且部分兒童暴露於室內二手菸狀態下，並未具有氣喘之表現；因此易感受性因子在氣喘的成因上的角色，值得進一步的觀察。香菸已被顯示可減少上皮細胞的黏附以及增加分離，而細胞黏附分子上皮細胞黏附蛋白(E-cadherin) 對於正常結構以及上皮組織的功能之形成與維持，扮演一個必要的角色，因此人類上皮細胞黏附蛋白基因 (CDH1) 可能相關於氣喘的發生。我們以一個醫院為基礎的病例對照研究檢視CD14 -159、CD14 -260 以及STAT6 G2964A、CDH1-160 基因多形性與兒童氣喘相關的假說，總計357 名兒童參與本研究。研究對象的個人特徵資料，是經由面對面的問卷訪視所收集；兒童的室內二手菸暴露量是以每天平均暴露的香菸支數計算，亦即父母親於兒童在家時，抽菸支數的總和。四種台灣常見過敏原也被執行皮膚測試加以判定；基因型則是以聚合酶鏈鎖反應(polymerase chain reaction [PCR]) 判定。我們的研究結果顯示，兒童氣喘發生顯著危險是相關於個體過敏原測試陽性以及CD14 -159、STAT6 G2964A、CDH1 -160 基因型。過敏原反應呈陽性並且攜帶CD14 -159 TT/CT 基因型 (RRm = 6.3; 95% CI = 2.0-20.4)、STAT6 G2964A AA/GA 基因型(RRm = 8.9; 95% CI = 2.8-27.9)、以及CDH1-160 AA/CA 基因型 (RRm = 19.9; 95% CI = 4.6-87.0) 的兒童分別相較於過敏原反應呈陰性且攜帶CD14 -159 CC 基因型、STAT6 GG 基因型、以及CDH1-160 CC 基因型的兒童有較高之氣喘發病危險性。進一步地，評估室內二手菸暴露與易感受性基因型對於氣喘發生之危險。相較於過敏原測試陽性攜帶CDH1-160 CC 基因型且每天暴露香菸支數0-5 支的兒童，攜帶CDH1-160 AA/CA 基因型且暴露香菸支數0-5 支的兒童、與每天暴露香菸支數大於5 支的兒童，分別呈現1.9 倍 (95% C.I. = 0.9-4.2) 與3.1 倍 (95% C.I. = 1.1-8.5) 的氣喘發生危險。我們的結果建議著表示，CD14、STAT6 和CDH1 易感受基因型可能調控過敏與二手菸暴露之兒童的氣喘發病歷程。 Type 2 T helper lymphocytes (Th2 cells) and their cytokine products are important in the pathogenesis of asthma. CD14 functions as a multifunctional receptor for bacterial cell wall components and is likely to play a role in the modulation of Th1-Th2 response during early childhood. Signal transducer and activator of transcription factor (Stat) 6 is a transcription factor essential for Th2 cell differentiation. The way passive smoking affects childhood asthma is still a mystery. A part of children at the indoor tobacco exposure were not have the asthma expression; therefore, the sensitive factor of a role at asthma will be observed. And cigarette smoke has been shown to decrease epithelial-cell adherence and to increase detachment, the cell adhesion molecule E-cadherin plays an essential role in the formation and maintenance of normal architecture and function of epithelial tissues; therefore, human CDH1 gene might be related to the cause of asthma. In the present study, the hypothesis that polymorphisms in the CD14 -159, CD14 -260, STAT6 G2964A and CDH1-160 genes are associated with childhood asthma were examined under a hospital-based case-control study. A total of 357 children were recruited into our study. Independent interviews with parents by our well-trained research assistants with a semi-structured clinical questionnaire during the study period. The smoking history of subject’s family members will be included the number of cigarettes smoked daily, and the duration the child was exposed to environmental tobacco smoke. Allergen test was performed by an intracutaneous skin test with Taiwan common aeroallergens. The genotypes of CD14 -159, CD14 -260, STAT6 G2964A and CDH1-160 were identified by polymerase chain reaction (PCR). Our results revealed that allergen test-positive children with the CD14 -159 TT/CT genotype (RRm = 6.3; 95% CI = 2.0-20.4), the STAT6 G2964A AA/GA genotype (RRm = 8.9; 95% CI = 2.8-27.9), and the CDH1 -160 AA/CA genotype (RRm = 19.9; 95% CI = 4.6-87.0) had a higher risk of asthma development than did allergen test-negative children with the CD14 -159 CC genotype, the STAT6 GG genotype, and CDH1-160 CC genotype, respectively. Further, assess the indoor tobacco exposure and sensitive genotype about the risk of asthma development. Children with the CDH1-160 AA/CA genotype and exposure 0-5 cigarettes smoked daily (RRm = 1.9; 95% CI = 0.9-4.2), and exposure surpassed in 5 cigarettes smoked daily (RRm = 3.1; 95% CI = 1.1-8.5) had a higher risk of asthma development than allergen test-positive children with the CDH1-160 CC genotype. These results suggested that susceptible CD14, STAT6 and CDH1 genotypes may modulate the asthma development in smoking-exposed children.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/3036
Appears in Collections:	[公共衛生學系暨碩士班] 研究計劃

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942314B040033.pdf	研究計畫成果報告	716Kb	Adobe PDF	407	View/Open
翁瑞宏.pdf	國科會計劃報告書	716Kb	Adobe PDF	772	View/Open

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