氣喘是一種孩童常見的慢性呼吸道發炎性疾病。吸入過敏原，如家庭塵瞞後，經由E型免疫球蛋白調控的過敏反應，而產生支氣管收縮。 呼吸道的T淋巴球、嗜酸性白血球、巨噬細胞、以及肥胖細胞浸潤現象，是一項重要的臨床特徵。在不同族群的一些基因關聯性研究中已指出，六號染色體短臂21 (6p21)的位置與氣喘或是過敏性疾病的發生有著密切相關。位於這段區域中的第二型人類白血球抗原、腫瘤壞死因子、與血小板活化因子乙醯水解脢都是造成氣喘的候選基因。而腫瘤壞死因子與血小板活化因子都是參與在呼吸道發炎反應中的重要介質。曾有研究發現，腫瘤壞死因子在氣喘病患痰液中表現增加。且其基因上相對於轉錄起始點的 –308位置若有 G→A的變異，也曾被指出會影響啟動子的轉錄活性。另外在 –863位置的 C→A變異則與較低量的腫瘤壞死因子表現有關。在我們實驗室先前的研究中發現，–308的基因多型性與氣喘發生有關，但–238的多型性卻沒有。除了這兩個點外，還有其他單一核甘酸多型性位置在我們的族群中被找到，如： -1031、-863、-857、及 –806。在本篇研究中發現，腫瘤壞死因子基因啟動子 -1031、-863、-857、及 –806這四個位置的基因多型性皆與氣喘發生有關聯，且這些位置間的交互作用會增加氣喘發生的危險機率。又在我們研究族群中，氣喘患者血清中腫瘤壞死因子表現量較對照組高。但無論是體內或是在周邊血液單核球經過敏原刺激的體外實驗中，我們並沒有發現這些腫瘤壞死因子基因多型性位置與其表現量有關聯性。
血小板活化因子是一種磷酸脂衍生出來的介質，最早是在經抗原刺激且被E型免疫球蛋白致敏化的嗜鹼性白血球中被發現的。它主要的作用是會造成血管收縮、支氣管收縮、以及增加白血球附著在內皮細胞上等發炎反應的特徵。而其在體內主要是受血小板活化因子乙醯水解脢的調控。某些位於血小板活化因子乙醯水解脢基因上的變異，已被指出與氣喘病患中較高的E型免疫球蛋白表現有關。又在我們的族群中，E型免疫球蛋白表現在氣喘孩童中較健康對照組為高。因此，本實驗針對三個血小板活化因子乙醯水解脢基因上的多型性: 位於第四表現序列中的Arg 92 His、第七表現序列中的 Ile 198 Thr、以及第十一表現序列中的Ala 379 Val，探討與氣喘發生和氣喘患者的血清中E型免疫球蛋白濃度之關係。但在我們的研究結果中，這些基因多型性與氣喘發生及氣喘患者的血清中E型免疫球蛋白濃度皆沒有關性.

Asthma is a chronic airway inflammation and is the most common disease of childhood. Bronchial constriction is initiated by IgE-mediated allergy to inhaled allergen such as house dust mite. It is characterized by T lymphocytes, eosinophils, macrophages and mast cells infiltration in the airway wall. Genetic linkage studies in various populations have indicated that chromosome 6p21 was associated with asthma and/or atopy. Within this region, HLA class Ⅱ gene, tumor necrosis factor α (TNFα) and platelet-activating factor acetylhydrolase (PAFAH) are candidate genes for asthma. TNFα and platelet-activating factor are among many mediators involved in the airway inflammation process. Increased levels of TNFα have been reported in sputum of asthmatics. G→A transition at –308 (relative to transcription start site) has been shown to affect promoter transcriptional activity. C→A substitution at –863 is associated with reduced circulating TNFα levels. In our previous study, TNFα promoter region –308 (G/A) polymorphism, but not –238 (G/A), is associated with asthma. Besides –308, several single nucleotide polymorphisms (SNP) also have been revealed at –1031, -863, -857, -806 in our study population. In this report, polymorphisms at –1031, -863, -857, -806 within TNFα promoter region are also associated with asthma. And the combined effects between these polymorphic sites increase the risk of asthma. In our study population, higher serum TNFα level was found in asthmatic group. But we failed to see the associations of the genetic polymorphisms of TNFα promoter with TNFα production in vivo or in vitro after peripheral mononuclear cells stimulated by mitogens.
The platelet-activating factor (PAF) is a phospholipid-derived mediator, originally discovered from antigen-stimulated IgE-sensitized basophils. It can cause vasoconstriction, bronchoconstriction, increased leukocyte adhesion to endothelium, chemotaxis, characteristic of inflammation. Its effects are controlled by PAF-acetylhydrolase (PAFAH). Variants of PAFAH gene were associated with total IgE concentration in asthmatics. Our studies have indicated that asthmatic children have a higher serum IgE levels compared with controls. Three variants of PAFAH gene, Arg92His (exon4), Ile198Thr (exon7), and Ala379Val (exon11) were examined for their associations with asthma and serum IgE levels in asthma patients. None of PAFAH gene polymorphisms was associated with asthma or with total IgE concentration in asthmatics in our studies.

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