Glutathione S-Transferase P1基因多型性、抽菸與成人氣喘之相關

The associations between Glutathione S-Transferase P1 polymorphisms, cigarette smoking and risk of asthma among adults

蕭茹鈴(Ru-Ling Hsiao)

指導教授 ： 王姿乃

高雄醫學大學/健康科學院/公共衛生學研究所/碩士(2012年)

https://doi.org/10.6832/KMU.2012.00067

摘要

研究背景：氣喘是一個重要的全球健康議題，表現在呼吸道上皮細胞的酵素，90%以上由麩胺基硫轉移酵素(Glutathione S-Transferase, GST)基因家族中的GSTP1基因所調控，有研究指出GSTP1基因多型性是氣喘與支氣管過度反應的新標記。
研究目的：本研究主要目標為分析GSTP1基因多型性與成人氣喘、肺功能、IgE濃度之間的相關性，並進一步探討抽菸、GSTP1基因型及單套基因型與氣喘的關係。
材料方法：本研究為病例對照研究，氣喘病人從醫院收案而來，與社區對照依年齡、性別1比1配對，共納入1048人，排除問卷篩檢自我回報為氣喘、肺炎、肺結核、肺氣腫、慢性阻塞性肺病、肺癌等肺部疾病或其他癌症的患者。從HapMap選取5個GSTP1的tagSNPs，分別為rs6591256、GSTP1 Ile105Val (rs1695)、rs749174、rs1871042、rs947895。所有研究對象皆完成問卷，且以即時聚合酶連鎖反應完成基因型鑑定。
研究結果：校正干擾因子後，曾經有抽菸習慣並且SNP1(rs6591256)帶AA型(AOR=2.58)、SNP2(rs1695)帶AA型(AOR=2.56)、SNP3(rs749174)帶GG型(AOR=2.49)、SNP4(rs1871042)帶CC型(AOR=2.47)以及SNP5(rs947895)帶CC型(AOR=2.47)會增加罹患氣喘的風險。曾經有抽菸習慣且SNP1(rs6591256)、SNP2(rs1695)、SNP4(rs1871042)單套基因型組合為h111(AAC)者，會增加罹患氣喘的風險(OR=1.93)。
結論：本研究結果指出，有抽菸習慣且GSTP1基因之tagSNPs帶major allele的同型合子或rs6591256-rs1695-rs1871042帶AAC單套基因型者會增加氣喘的風險；因此，抽菸和GSTP1基因在成人氣喘扮演重要的角色。未來可依香菸暴露量、氣喘嚴重度分層，或是測量體內GST酵素活性，亦可進行GST基因家族間(gene-gene)的交互作用，深入探討GSTP1基因與氣喘的關係。

關鍵字

氣喘 ； 單一核苷酸多型性 ； 抽菸 ； 單套基因型

並列摘要

Background：Asthma is a global public health issue. There is more than 90% of GST enzyme activity encoded by GSTP1 gene in human lung epithelium. Previous studies have reported that a single nucleotide polymorphism (SNP) of GSTP1 is a new marker for identifying bronchial hyperresponsiveness and asthma.

Objective：The aim of the present study was to explore the association between polymorphisms of GSTP1 gene and asthma, and to determine whether the relationship between GSTP1 gene and asthma was modified by smoking habit. We also investigated the association between GSTP1 genotype, lung function and IgE concentrations in adult asthma.

Materials and methods：524 hospital based asthmatic adults and 524 age and sex matched community controls were recruited in the present case-control study, and the controls were free from asthma, pneumonia, tuberculosis, emphysema, COPD and cancers by self-report. We selected five tagSNPs which included GSTP1 rs6591256, GSTP1 Ile105Val (rs1695), rs749174, rs1871042 and rs947895 from HapMap website. All subjects completed a questionnaire and were genotyped by using real-time PCR.

Results：After controlling for confounding factors, the smokers carried major homozygous allele for five SNPs had a significantly increase risk of asthma (AOR=2.58, 2.56, 2.49, 2.47 and 2.47 for GSTP1 rs6591256, rs1695, rs749174, rs1871042 and rs947895, respectively). The haplotype analyses showed an increasing risk for the major allele (AAC) of rs6591256-rs1695-rs1871042 on asthma (OR=1.93) in ever-smokers, but not in never smokers.

Conclusion：Among ever-smokers, major homozygous carriers and the haplotype (AAC) of GSTP1 tagSNPs are associated with an increasing risk of asthma. The results suggested that cigarette smoking and GSTP1 gene may play important roles in adult asthma.

並列關鍵字

asthma ； single-nucleotide polymorphism ； cigarette smoking ； haplotype

參考文獻

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