Glutathione S-Transferase Genotype Protects against In Utero Tobacco–linked Lung Function Deficits

Louisa Owens (Corresponding Author), Ingrid A. Laing, Jasminka Murdzosk, Guicheng Zhang, Steve W. Turner, Peter N. le Souëf

Research output: Contribution to journalArticle

2 Citations (Scopus)
4 Downloads (Pure)

Abstract

Rationale

In utero tobacco exposure is associated with reduced infant lung function. Anti-oxidant enzymes from the glutathione-s-transferase (GST) family may protect against these lung function deficits.

Objectives:

(1) Assess the long-term effect of in utero smoke exposure on lung function into adulthood.

(2) Assess whether GSTT1 and GSTM1 active genotypes have longterm protective effects on lung function.

Methods:

In this longitudinal study, based on a normal population (n=253), lung function was measured during infancy and then at 6, 11, 18 and 24 years. GSTM1 and GSTT1 genotype was analysed in a subgroup (n= 179). Lung function was assessed longitudinally from 6 to 24 years (n=144).

Main Results

Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC from 6 to 24 years (mean difference – 3.87% predicted, p=0.021; -3.35% predicted, p=0.035, respectively). Among those homozygous for the GSTM1 null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference -6.2% predicted, p=0.01; -4.7% predicted, p=0.043 respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1 null and GSTT1 active genotypes.

Conclusions

GST genotypes may have protective effects against the deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in anti-oxidant pathways for at-risk infants of smoking mothers.
Original languageEnglish
Pages (from-to)462-470
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume200
Issue number4
Early online date6 Feb 2019
DOIs
Publication statusPublished - 15 Aug 2019

Fingerprint

Glutathione Transferase
Genotype
Tobacco
Lung
Mothers
Oxidants
Smoke
Longitudinal Studies
Smoking
Enzymes
Population

Keywords

  • respiratory function tests
  • detoxification
  • gene-environment interaction
  • tobacco smoke pollution
  • population genetics
  • Detoxification
  • Gene-environment interaction
  • Tobacco smoke pollution
  • Population genetics
  • Respiratory function tests
  • STANDARDIZATION
  • MU
  • CHILDHOOD
  • LOCUS
  • SMOKE EXPOSURE
  • POLYMORPHISMS
  • ASTHMA
  • MATERNAL SMOKING

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Pulmonary and Respiratory Medicine

Cite this

Glutathione S-Transferase Genotype Protects against In Utero Tobacco–linked Lung Function Deficits. / Owens, Louisa (Corresponding Author); Laing, Ingrid A.; Murdzosk, Jasminka; Zhang, Guicheng; Turner, Steve W.; le Souëf, Peter N.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 200, No. 4, 15.08.2019, p. 462-470.

Research output: Contribution to journalArticle

Owens, Louisa ; Laing, Ingrid A. ; Murdzosk, Jasminka ; Zhang, Guicheng ; Turner, Steve W. ; le Souëf, Peter N. / Glutathione S-Transferase Genotype Protects against In Utero Tobacco–linked Lung Function Deficits. In: American Journal of Respiratory and Critical Care Medicine. 2019 ; Vol. 200, No. 4. pp. 462-470.
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title = "Glutathione S-Transferase Genotype Protects against In Utero Tobacco–linked Lung Function Deficits",
abstract = "RationaleIn utero tobacco exposure is associated with reduced infant lung function. Anti-oxidant enzymes from the glutathione-s-transferase (GST) family may protect against these lung function deficits.Objectives:(1) Assess the long-term effect of in utero smoke exposure on lung function into adulthood.(2) Assess whether GSTT1 and GSTM1 active genotypes have longterm protective effects on lung function.Methods:In this longitudinal study, based on a normal population (n=253), lung function was measured during infancy and then at 6, 11, 18 and 24 years. GSTM1 and GSTT1 genotype was analysed in a subgroup (n= 179). Lung function was assessed longitudinally from 6 to 24 years (n=144).Main ResultsExposure to maternal in utero tobacco was associated with lower FEV1 and FVC from 6 to 24 years (mean difference – 3.87{\%} predicted, p=0.021; -3.35{\%} predicted, p=0.035, respectively). Among those homozygous for the GSTM1 null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference -6.2{\%} predicted, p=0.01; -4.7{\%} predicted, p=0.043 respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1 null and GSTT1 active genotypes.ConclusionsGST genotypes may have protective effects against the deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in anti-oxidant pathways for at-risk infants of smoking mothers.",
keywords = "respiratory function tests, detoxification, gene-environment interaction, tobacco smoke pollution, population genetics, Detoxification, Gene-environment interaction, Tobacco smoke pollution, Population genetics, Respiratory function tests, STANDARDIZATION, MU, CHILDHOOD, LOCUS, SMOKE EXPOSURE, POLYMORPHISMS, ASTHMA, MATERNAL SMOKING",
author = "Louisa Owens and Laing, {Ingrid A.} and Jasminka Murdzosk and Guicheng Zhang and Turner, {Steve W.} and {le Sou{\"e}f}, {Peter N.}",
note = "We would like to thank all the previous contributors to the Perth Infant Asthma Follow up study including David Mullane, Desmond Cox, Kimberley Franks, Lou Landau, Jack Goldblatt, Sally Young, Siew-Kim Khoo, Neil Gibson, Veena Judge, Lyle Palmer, Paul O’Keefe, Jackie Arnott, Steve Stick, Peter Rye, Catherine Hayden and Sunalene Devadason.",
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T1 - Glutathione S-Transferase Genotype Protects against In Utero Tobacco–linked Lung Function Deficits

AU - Owens, Louisa

AU - Laing, Ingrid A.

AU - Murdzosk, Jasminka

AU - Zhang, Guicheng

AU - Turner, Steve W.

AU - le Souëf, Peter N.

N1 - We would like to thank all the previous contributors to the Perth Infant Asthma Follow up study including David Mullane, Desmond Cox, Kimberley Franks, Lou Landau, Jack Goldblatt, Sally Young, Siew-Kim Khoo, Neil Gibson, Veena Judge, Lyle Palmer, Paul O’Keefe, Jackie Arnott, Steve Stick, Peter Rye, Catherine Hayden and Sunalene Devadason.

PY - 2019/8/15

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N2 - RationaleIn utero tobacco exposure is associated with reduced infant lung function. Anti-oxidant enzymes from the glutathione-s-transferase (GST) family may protect against these lung function deficits.Objectives:(1) Assess the long-term effect of in utero smoke exposure on lung function into adulthood.(2) Assess whether GSTT1 and GSTM1 active genotypes have longterm protective effects on lung function.Methods:In this longitudinal study, based on a normal population (n=253), lung function was measured during infancy and then at 6, 11, 18 and 24 years. GSTM1 and GSTT1 genotype was analysed in a subgroup (n= 179). Lung function was assessed longitudinally from 6 to 24 years (n=144).Main ResultsExposure to maternal in utero tobacco was associated with lower FEV1 and FVC from 6 to 24 years (mean difference – 3.87% predicted, p=0.021; -3.35% predicted, p=0.035, respectively). Among those homozygous for the GSTM1 null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference -6.2% predicted, p=0.01; -4.7% predicted, p=0.043 respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1 null and GSTT1 active genotypes.ConclusionsGST genotypes may have protective effects against the deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in anti-oxidant pathways for at-risk infants of smoking mothers.

AB - RationaleIn utero tobacco exposure is associated with reduced infant lung function. Anti-oxidant enzymes from the glutathione-s-transferase (GST) family may protect against these lung function deficits.Objectives:(1) Assess the long-term effect of in utero smoke exposure on lung function into adulthood.(2) Assess whether GSTT1 and GSTM1 active genotypes have longterm protective effects on lung function.Methods:In this longitudinal study, based on a normal population (n=253), lung function was measured during infancy and then at 6, 11, 18 and 24 years. GSTM1 and GSTT1 genotype was analysed in a subgroup (n= 179). Lung function was assessed longitudinally from 6 to 24 years (n=144).Main ResultsExposure to maternal in utero tobacco was associated with lower FEV1 and FVC from 6 to 24 years (mean difference – 3.87% predicted, p=0.021; -3.35% predicted, p=0.035, respectively). Among those homozygous for the GSTM1 null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference -6.2% predicted, p=0.01; -4.7% predicted, p=0.043 respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1 null and GSTT1 active genotypes.ConclusionsGST genotypes may have protective effects against the deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in anti-oxidant pathways for at-risk infants of smoking mothers.

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KW - population genetics

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KW - Gene-environment interaction

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KW - Respiratory function tests

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KW - MU

KW - CHILDHOOD

KW - LOCUS

KW - SMOKE EXPOSURE

KW - POLYMORPHISMS

KW - ASTHMA

KW - MATERNAL SMOKING

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