GSTP1多态性和烟草烟雾暴露在儿童急性哮喘中的作用
2010/12/16
摘要
背景：谷胱甘肽-S -转移酶(GSTs)在对环境烟草烟雾（ETS）的解毒过程中起到重要作用，而ETS可造成气道炎症（哮喘的一个重要表现）。GST基因的遗传变异有可能影响个体对环境污染物的解毒。
目的：研究GSTP1多态性（Ile105Val和Ala114Val）单独及与ETS暴露联合，对过敏症和哮喘严重程度的影响。
方法：检测GSTP1 的基因型（Ile105Val和 Ala114Val），通过对父母进行问卷调查评价ETS暴露，后者通过检测尿液可替宁来进行证实。评价ETS暴露水平、GSTP1多态性及其相互作用对过敏症和哮喘严重程度的影响。
结果：对功能性GSTP1 105单核苷酸多态性，Ile/Ile基因型患者与其它基因型相比，当单独对基因型进行评价时，其对过敏症的优势比为2.77（P=0.054），若联合ETS暴露水平进行评价，其优势比增加至9.02（P=0.050）。与此类似，Ala/Ala 基因型患者与GSTP1 114其它基因型的患儿相比，当单独对基因型进行评价时，其过敏症风险增加5.47倍(P=0.002)，若联合ETS暴露水平进行评价，其风险增加9.17倍。所有105 Ile/Ile基因型患儿具有AA单体型（105 Ile/Ile和114 Ala/Ala），因此过敏症的优势比相同。与至少有一个*C 单体型的患儿及未ETS暴露的患儿相比，无任何*C 单体型的患儿（105 Val和114 Val等位基因），ETS暴露能使过敏症的患病风险增加9.17倍(P=0.020)。
结论：GSTP1核苷酸多态性、过敏症和ETS暴露之间存在显著相关性。
（刘国梁 审校）
J Asthma. 2010 Sep 22. [Epub ahead of print]
The role of GSTP1 polymorphisms and tobacco smoke exposure in children with acute asthma.
Schultz EN, Devadason SG, Khoo SK, Zhang G, Bizzintino JA, Martin AC, Goldblatt J, Laing IA, Le Souëf PN, Hayden CM.
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
Abstract
Background. 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. Objective. To examine the role of polymorphisms in GSTP1 (Ile105Val and Ala114Val), alone and in combination with ETS exposure, on atopy and asthma severity. Methods. 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. Results. 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). Conclusion. There were significant interactions between GSTP1 SNPs, atopy, and ETS exposure in this cohort.
J Asthma. 2010 Sep 22. [Epub ahead of print]
背景：谷胱甘肽-S -转移酶(GSTs)在对环境烟草烟雾（ETS）的解毒过程中起到重要作用，而ETS可造成气道炎症（哮喘的一个重要表现）。GST基因的遗传变异有可能影响个体对环境污染物的解毒。
目的：研究GSTP1多态性（Ile105Val和Ala114Val）单独及与ETS暴露联合，对过敏症和哮喘严重程度的影响。
方法：检测GSTP1 的基因型（Ile105Val和 Ala114Val），通过对父母进行问卷调查评价ETS暴露，后者通过检测尿液可替宁来进行证实。评价ETS暴露水平、GSTP1多态性及其相互作用对过敏症和哮喘严重程度的影响。
结果：对功能性GSTP1 105单核苷酸多态性，Ile/Ile基因型患者与其它基因型相比，当单独对基因型进行评价时，其对过敏症的优势比为2.77（P=0.054），若联合ETS暴露水平进行评价，其优势比增加至9.02（P=0.050）。与此类似，Ala/Ala 基因型患者与GSTP1 114其它基因型的患儿相比，当单独对基因型进行评价时，其过敏症风险增加5.47倍(P=0.002)，若联合ETS暴露水平进行评价，其风险增加9.17倍。所有105 Ile/Ile基因型患儿具有AA单体型（105 Ile/Ile和114 Ala/Ala），因此过敏症的优势比相同。与至少有一个*C 单体型的患儿及未ETS暴露的患儿相比，无任何*C 单体型的患儿（105 Val和114 Val等位基因），ETS暴露能使过敏症的患病风险增加9.17倍(P=0.020)。
结论：GSTP1核苷酸多态性、过敏症和ETS暴露之间存在显著相关性。
（刘国梁 审校）
J Asthma. 2010 Sep 22. [Epub ahead of print]
The role of GSTP1 polymorphisms and tobacco smoke exposure in children with acute asthma.
Schultz EN, Devadason SG, Khoo SK, Zhang G, Bizzintino JA, Martin AC, Goldblatt J, Laing IA, Le Souëf PN, Hayden CM.
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
Abstract
Background. 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. Objective. To examine the role of polymorphisms in GSTP1 (Ile105Val and Ala114Val), alone and in combination with ETS exposure, on atopy and asthma severity. Methods. 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. Results. 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). Conclusion. There were significant interactions between GSTP1 SNPs, atopy, and ETS exposure in this cohort.
J Asthma. 2010 Sep 22. [Epub ahead of print]
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