- 期刊
Association of p53 Codon 72 Polymorphisms with Chronic Obstructive Pulmonary Disease
p53 condon 72基因多形性與慢性阻塞性肺病之間的關聯性
摘要
前言：慢性阻塞性肺病的形成與環境物質的刺激（尤其是抽煙）以及個體的遺傳特質有關聯。抽煙除了引起發炎反應，與慢性阻塞性肺病的形成可能有關之外，抽煙本身也可能形成氣管上皮構造的改變。而p53基因的多形性與其控制後天的(acquired)體質突變(somatic mutation)，可能可以部分解釋外在環境因子對於個體造成影響的敏感性(susceptibility)差異，其中包括了慢性阻塞性肺病。因此我們研究p53基因多形性與慢性阻塞性肺病感受性之間的關連。 方法：我們收集七十位慢性阻塞性肺病病人與六十四位健康的抽煙者。使用對偶基因專一性(allele-specific)的聚合脾鍊反應(PCR; polymerase chain reaction)技術來進行p53基因的多形性分析。對偶基因專一性(allele-specific)的PCR技術是經由直接的雙去氧(dideoxy)而定出PCR產物的序列來核對。 結果：利用聚合脾鍊反應－限制性片段長度多型性[PCR-RFLP (restriction fragment length polymorphism)]的技術分析周邊血液淋巴球genomic DNA純化出來的基因序列。p53基因型的分佈頻率在慢性阻塞性肺病病人與對照組有有明顯的不同。慢性阻塞性肺病病人有較高頻率p53 Pro/Pro及Arg/Pro基因型，相對於吸煙的健康人Arg/Arg基因型[OR=2.50, 95% CI 1.47-4.49, p=0.008]。 結論：我們認為，與吸煙有關之慢性阻塞性肺病和p53基因多形性有顯著的關聯。
並列摘要
Background: Polymorphisms in the genes controlling acquired somatic mutations may explain some of the observed differences in susceptibility to chronic obstructive pulmonary disease (COPD) caused by cigarettes. Thus, we investigated the relationship between the p53 codon 72 polymorphism and susceptibility to COPD. Methods and patients: Seventy patients with COPD and 64 healthy-smoker subjects were included. Polymorphisms of the p53 block were delineated using an allele-specific polymerase chain reaction (PCR) approach. The allele-specific PCR technique was verified by direct dideoxy sequencing of PCR products. Results: The genotype was analyzed using the polymerase chain reaction-restriction fragment length polymorphism technique with genomic DNA isolated from peripheral blood lymphocytes. The distribution frequencies of genotypes of the p53 codon 72 polymorphism were significantly different between the COPD and the control groups. Higher odds ratios (ORs) for COPD were seen for individuals with p53 Pro/Pro and Arg/Pro genotypes against Arg/Arg genotype [OR=2.50, 95% Cl 1.47-4.49, p=0.008]. Conclusion: The p53 codon 72 polymorphism was significantly associated with the presence of smoking-related COPD.
延伸閱讀
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