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Am J Respir Crit Care Med. 2019 Aug 15;200(4):462-470. doi: 10.1164/rccm.201807-1332OC.

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

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1School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
2School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
3Telethon Kids Institute, Subiaco, Western Australia, Australia.
4School of Public Health, Curtin University, Bentley, Western Australia, Australia.
5Centre for Genetic Origins of Health and Disease, University of Western Australia and Curtin University, Western Australia, Australia; and.
6Child Health, University of Aberdeen, Aberdeen, United Kingdom.


Rationale: In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally 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: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.


detoxification; gene–environment interaction; population genetics; respiratory function tests; tobacco smoke pollution


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