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Interaction of Glutathione S-Transferase M1, T1, and P1 Genes With Early Life Tobacco Smoke Exposure on Lung Function in Adolescents.

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 ≤ .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. TRIAL REGISTRY:Australian and New Zealand Clinical Trials Registry; No.: ACTRN12609000734268; URL: http://www.anzctr.org.au/.

journal_name

Chest

journal_title

Chest

authors

Dai X,Dharmage SC,Bowatte G,Waidyatillake NT,Perret JL,Hui J,Erbas B,Abramson MJ,Lowe AJ,Burgess JA,Svanes C,Lodge CJ

doi

10.1016/j.chest.2018.08.1079

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

94-102

issue

eissn

0012-3692

issn

1931-3543

pii

S0012-3692(18)32441-3

journal_volume

155

pub_type

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Interaction of Glutathione S-Transferase M1, T1, and P1 Genes With Early Life Tobacco Smoke Exposure on Lung Function in Adolescents.