Glutathione <i>S</i>-Transferase Genotype Protects against <i>In Utero</i> Tobacco-linked Lung Function Deficits.

Abstract

<b>Rationale:</b><i>In utero</i> tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione <i>S</i>-transferase (GST) family may protect against these lung function deficits.<b>Objectives:</b> To assess the long-term effect of <i>in utero</i> smoke exposure on lung function into adulthood, and to assess whether <i>GSTT1</i> and <i>GSTM1</i> active genotypes have long-term protective effects on lung function.<b>Methods:</b> In this longitudinal study based on a general population (<i>n</i> = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. <i>GSTM1</i> and <i>GSTT1</i> genotype was analyzed in a subgroup (<i>n</i> = 179). Lung function was assessed longitudinally from 6 to 24 years (<i>n</i> = 199).<b>Measurements and Main Results:</b> Exposure to maternal <i>in utero</i> tobacco was associated with lower FEV₁ and FVC longitudinally from 6 to 24 years (mean difference, -3.87% predicted, <i>P</i> = 0.021; -3.35% predicted, <i>P</i> = 0.035, respectively). Among those homozygous for the <i>GSTM1-</i>null genotype, <i>in utero</i> tobacco exposure was associated with lower FEV₁ and FVC compared with those with no <i>in utero</i> tobacco exposure (mean difference, -6.2% predicted, <i>P</i> = 0.01; -4.7% predicted, <i>P</i> = 0.043, respectively). For those with <i>GSTM1</i> active genotype, there was no difference in lung function whether exposed to maternal <i>in utero</i> tobacco or not. <i>In utero</i> tobacco exposure was associated with deficits in lung function among those with both <i>GSTT1-</i>null and <i>GSTT1</i>-active genotypes.<b>Conclusions:</b> Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with <i>in utero</i> tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.