谷胱甘肽S-转移酶M1、T1及P1基因与早期烟雾暴露对青少年肺功能的影响
2019/01/09
摘要
背景：谷胱甘肽S-转移酶（GST）基因参与肺部氧化应激调控。我们的目的是确定它们是否会改变早期烟雾暴露与不良肺部病变结果之间的关系。
方法：此墨尔本特应性队列研究（一个高风险出生队列）入组620名儿童，并自出生起进行前瞻性随访。收集数据包括围产期烟雾暴露史、哮喘病史、及第12（59％）年和第18年（66％）的肺功能，并对GST进行基因分型为M1、T1和P1（69％）。
结果：发现GST基因与烟雾暴露相互作用影响肺功能（P<0.05）。只有在未表达GSTT1基因型的儿童中，早年存在来自母亲，父亲或父母的烟雾暴露史与第12年和第18年发生FEV1及FVC（使用支气管扩张剂前）下降的风险上升有关。 表达GSTT1基因型的儿童未发现此相关性。 同样，只有在未表达GSTM1基因型的儿童中，存在来自父亲或父母烟雾暴露与第18年 FEV1和FVC下降（使用支气管舒张剂前后）相关。仅在表达GSTP1 Ile / Ile基因型的儿童中，存在母亲烟雾暴露史与第18年FEV1降低的风险增加有关，但表达Val / Val或Ile / Val基因型的患儿情况并非如此。
结论：此研究为早期烟雾暴露与GST基因型对肺功能的相互作用提供了证据。未携带GST基因或携带GSTP1 Ile / Ile等位基因儿童早年存在烟雾暴露更容易受到影响。此研究发现提出强有力的建议：保护婴儿免受烟雾暴露。
Interaction of Glutathione S-Transferase M1, T1, and P1 Genes With Early Life Tobacco Smoke Exposure on Lung Function in Adolescents
Xin Dai, Shyamali C. Dharmage, Gayan Bowatte.
Abstract
BACKGROUND: Glutathione S-transferase (GST) genes are involved in the management of oxidative stress in the lungs. We aimed to determine whether they modify the associations between early life smoke exposure and adverse lung health outcomes.
METHODS: The Melbourne Atopy Cohort study (a high-risk birth cohort) enrolled 620 children and followed them prospectively from birth. We recorded perinatal tobacco smoke exposure, asthma, and lung function at 12 (59%) and 18 years (66%) and genotyped for GSTM1, GSTT1, and GSTP1 (69%).
RESULTS: GST genotypes were found to interact with tobacco smoke exposure on lung function outcomes (P interaction <0.05). Only among children with GSTT1 null genotypes was exposure to mother’s, father’s, or parental tobacco smoke in early life associated with an increased risk of reductions in prebronchodilator (BD) FEV1 and FVC at both 12 and 18 years. These associations were not seen in children with GSTT1 present. Similarly, only among children with GSTM1 null genotypes was exposure to father’s or parental smoking associated with reductions in pre- and post-BD FEV1 and FVC at 18 years. Only among children with Ile/Ile genotypes of GSTP1 was exposure to mother’s smoking associated with increased risk of reduced FEV1 at 18 years, but this was not the case among children with Val/Val or Ile/Val genotypes.
CONCLUSIONS: Our study provides evidence of interaction between early tobacco smoke exposure and GST genotypes on lung function. Carriers of GST null mutations and GSTP1 Ile/Ile alleles may be more susceptible when exposed to tobacco smoke in early life. These findings support stronger recommendations to protect all infants from tobacco smoke exposure.
背景：谷胱甘肽S-转移酶（GST）基因参与肺部氧化应激调控。我们的目的是确定它们是否会改变早期烟雾暴露与不良肺部病变结果之间的关系。
方法：此墨尔本特应性队列研究（一个高风险出生队列）入组620名儿童，并自出生起进行前瞻性随访。收集数据包括围产期烟雾暴露史、哮喘病史、及第12（59％）年和第18年（66％）的肺功能，并对GST进行基因分型为M1、T1和P1（69％）。
结果：发现GST基因与烟雾暴露相互作用影响肺功能（P<0.05）。只有在未表达GSTT1基因型的儿童中，早年存在来自母亲，父亲或父母的烟雾暴露史与第12年和第18年发生FEV1及FVC（使用支气管扩张剂前）下降的风险上升有关。 表达GSTT1基因型的儿童未发现此相关性。 同样，只有在未表达GSTM1基因型的儿童中，存在来自父亲或父母烟雾暴露与第18年 FEV1和FVC下降（使用支气管舒张剂前后）相关。仅在表达GSTP1 Ile / Ile基因型的儿童中，存在母亲烟雾暴露史与第18年FEV1降低的风险增加有关，但表达Val / Val或Ile / Val基因型的患儿情况并非如此。
结论：此研究为早期烟雾暴露与GST基因型对肺功能的相互作用提供了证据。未携带GST基因或携带GSTP1 Ile / Ile等位基因儿童早年存在烟雾暴露更容易受到影响。此研究发现提出强有力的建议：保护婴儿免受烟雾暴露。
（中日友好医院呼吸与危重症医学科 张鑫 摘译 林江涛 摘译）
（Chest. 155#1 JANUARY 2019）
（Chest. 155#1 JANUARY 2019）
Interaction of Glutathione S-Transferase M1, T1, and P1 Genes With Early Life Tobacco Smoke Exposure on Lung Function in Adolescents
Xin Dai, Shyamali C. Dharmage, Gayan Bowatte.
Abstract
BACKGROUND: Glutathione S-transferase (GST) genes are involved in the management of oxidative stress in the lungs. We aimed to determine whether they modify the associations between early life smoke exposure and adverse lung health outcomes.
METHODS: The Melbourne Atopy Cohort study (a high-risk birth cohort) enrolled 620 children and followed them prospectively from birth. We recorded perinatal tobacco smoke exposure, asthma, and lung function at 12 (59%) and 18 years (66%) and genotyped for GSTM1, GSTT1, and GSTP1 (69%).
RESULTS: GST genotypes were found to interact with tobacco smoke exposure on lung function outcomes (P interaction <0.05). Only among children with GSTT1 null genotypes was exposure to mother’s, father’s, or parental tobacco smoke in early life associated with an increased risk of reductions in prebronchodilator (BD) FEV1 and FVC at both 12 and 18 years. These associations were not seen in children with GSTT1 present. Similarly, only among children with GSTM1 null genotypes was exposure to father’s or parental smoking associated with reductions in pre- and post-BD FEV1 and FVC at 18 years. Only among children with Ile/Ile genotypes of GSTP1 was exposure to mother’s smoking associated with increased risk of reduced FEV1 at 18 years, but this was not the case among children with Val/Val or Ile/Val genotypes.
CONCLUSIONS: Our study provides evidence of interaction between early tobacco smoke exposure and GST genotypes on lung function. Carriers of GST null mutations and GSTP1 Ile/Ile alleles may be more susceptible when exposed to tobacco smoke in early life. These findings support stronger recommendations to protect all infants from tobacco smoke exposure.
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