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In Utero Smoke Exposure and Role of Maternal and Infant Glutathione S-Transferase Genes on Airway Responsiveness and Lung Function in Infancy

¹ School of Paediatrics and Child Health, University of Western Australia, Perth, Australia

Correspondence and requests for reprints should be addressed to Ms. Jasminka Murdzoska, BSc (Hons), School of Pediatrics and Child Health, University of Western Australia, Princess Margaret Hospital, Roberts Road, Subiaco WA 6008, Perth, Australia. E-mail: jmurdzoska{at}meddent.uwa.edu.au

Rationale: Xenobiotics in the maternal circulation are capable of crossing the placental barrier so a reduction in the mother and fetus's detoxification ability due to genetic variation in the glutathione S-transferases (GSTs) could expose the fetus to higher levels of toxins.

Objectives: To investigate the interactive effects of maternal smoking during pregnancy with maternal and infant GST genotypes on airway responsiveness (AR) and lung function in infancy.

Methods: GSTT1, GSTP1 and GSTM1 were genotyped in infants and mothers, in utero smoke exposure was evaluated by questionnaire, AR was assessed by histamine challenge and max_FRC was measured using the rapid thoracoabdominal compression technique. We investigated the interactive effects of maternal smoking during pregnancy with maternal and infant GST genes on AR and lung function at 1, 6, and 12 months and longitudinally throughout the first year.

Measurements and Main Results: Infant and/or maternal GSTT1 nonnull was associated with reduced AR at 12 months and throughout the first year and increased max_FRC at 6 months. Maternal GSTP1 Val/Val or Ile/Val was associated with increased max_FRC at 6 months. In infants exposed to in utero smoke, infant and/or maternal GSTT1 nonnull was associated with reduced AR at 1 month and throughout the first year and increased max_FRC throughout the first year. Maternal GSTP1 Val/Val or Ile/Val was associated with increased max_FRC at 6 months.

Conclusions: GST genes may be especially important during fetal development as they may modify, through proficient detoxification, the effects of in utero maternal smoke exposure on AR and lung function in infants.

Key Words: infant lung function • airway responsiveness • GST genes • maternal smoking during pregnancy

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The effects of in utero smoke exposure on infant lung health may be modulated by maternal and infant glutathione S-transferase (GST) detoxifying genes. What This Study Adds to the Field Associations between maternal and infant GSTT1 and GSTP1 in combination with in utero smoke exposure on infant airway responsiveness and lung function suggests an important role for GST genes in detoxifying tobacco smoke constituents in utero, thereby influencing infant respiratory health.