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

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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.


(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.


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.


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
Issue number4
Early online date6 Feb 2019
Publication statusPublished - 15 Aug 2019

Bibliographical 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.


  • respiratory function tests
  • detoxification
  • gene-environment interaction
  • tobacco smoke pollution
  • population genetics
  • Detoxification
  • Gene-environment interaction
  • Tobacco smoke pollution
  • Population genetics
  • Respiratory function tests
  • MU


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