Schultz En Nee, Devadason Sunalene G, Khoo Siew-Kim, Zhang Guicheng, Bizzintino Joelene A, Martin Andrew C, Goldblatt Jack, Laing Ingrid A, Le Souëf Peter N, Hayden Catherine M
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
J Asthma. 2010 Nov;47(9):1049-56. doi: 10.1080/02770903.2010.508856.
The glutathione S-transferase enzymes (GSTs) play an important role in the detoxification of environmental tobacco smoke (ETS), which contributes to airway inflammation, a key component of asthma. Genetic variation in GST genes may influence individuals' ability to detoxify environmental pollutants.
To examine the role of polymorphisms in GSTP1 (Ile105Val and Ala114Val), alone and in combination with ETS exposure, on atopy and asthma severity.
GSTP1 Ile105Val and Ala114Val were genotyped and ETS exposure was assessed by parental questionnaire, which was validated by urinary cotinine measurements. Associations between ETS exposure, GSTP1 polymorphisms, and their interaction on atopy and asthma severity were investigated.
For the functional GSTP1 105 SNP, those with the Ile/Ile genotype had odds for atopy of 2.77 (p = .054) when assessed by genotype alone, which increased to 9.02 (p = .050) when ETS was included, relative to individuals with other genotypes. Likewise, compared to children with other GSTP1 114 genotypes, those with Ala/Ala genotype had a 5.47-fold (p = .002) increased risk of atopy (p = .020) when assessed by genotype alone, increasing to 9.17-fold when ETS was included. The 105 Ile/Ile individuals all had the AA (105 Ile/Ile and 114 Ala/Ala) haplotype group; therefore, the odds for atopy were the same. Individuals without any *C haplotype (105 Val and 114 Val allele) who were exposed to ETS had a 9.17-fold increased risk of atopy when compared with individuals with at least one *C haplotype and not exposed to ETS (p = .020).
There were significant interactions between GSTP1 SNPs, atopy, and ETS exposure in this cohort.
谷胱甘肽S-转移酶（GSTs）在环境烟草烟雾（ETS）的解毒过程中发挥重要作用，而ETS会导致气道炎症，这是哮喘的一个关键组成部分。GST基因的遗传变异可能会影响个体对环境污染物的解毒能力。
研究GSTP1基因多态性（Ile105Val和Ala114Val）单独以及与ETS暴露共同作用对特应性和哮喘严重程度的影响。
对GSTP1 Ile105Val和Ala114Val进行基因分型，并通过家长问卷评估ETS暴露情况，该问卷通过尿可替宁测量进行了验证。研究了ETS暴露、GSTP1基因多态性及其相互作用对特应性和哮喘严重程度的影响。
对于功能性GSTP1 105单核苷酸多态性（SNP），仅按基因型评估时，Ile/Ile基因型个体患特应性的比值比为2.77（p = 0.054），当纳入ETS因素时，相对于其他基因型个体，该比值比增至9.02（p = 0.050）。同样地，与其他GSTP1 114基因型的儿童相比，仅按基因型评估时，Ala/Ala基因型个体患特应性的风险增加了5.47倍（p = 0.002），纳入ETS因素时增至9.17倍（p = 0.020）。105位Ile/Ile个体均属于AA（105 Ile/Ile和114 Ala/Ala）单倍型组；因此，患特应性的比值比相同。与至少有一个C单倍型且未暴露于ETS的个体相比，暴露于ETS且无任何C单倍型（105 Val和114 Val等位基因）的个体患特应性的风险增加了9.17倍（p = 0.020）。
在该队列中，GSTP1单核苷酸多态性、特应性和ETS暴露之间存在显著的相互作用。
