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 Vmax(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 Vmax(FRC) at 6 months. Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(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 Vmax(FRC) throughout the first year. Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(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.
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 Vmax(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 Vmax(FRC) at 6 months. Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(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 Vmax(FRC) throughout the first year. Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(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.
Authors: Cindy T McEvoy; Kristin F Milner; Ashley J Scherman; Diane G Schilling; Christina J Tiller; Brittany Vuylsteke; Lyndsey E Shorey-Kendrick; Eliot R Spindel; Robert Schuff; Julie Mitchell; Dawn Peters; Jill Metz; David Haas; Keith Jackson; Robert S Tepper; Cynthia D Morris Journal: Contemp Clin Trials Date: 2017-05-08 Impact factor: 2.226
Authors: Steve Turner; Ben Francis; Nuha Wani; Susanne Vijverberg; Maria Pino-Yanes; Somnath Mukhopadhyay; Roger Tavendale; Colin Palmer; Esteban G Burchard; Simon Kebede Merid; Erik Melén; Anke H Maitland-van der Zee; On Behalf Of The Pharmacogenomics In Childhood Asthma Consortium Journal: Pharmacogenomics Date: 2018-05-22 Impact factor: 2.533
Authors: Andrew Bush; Thomas Ferkol; Algirdas Valiulis; Artur Mazur; Ivane Chkhaidze; Tamaz Maglakelidze; Sergey Sargsyan; Gevorg Boyajyan; Olga Cirstea; Svitlana Doan; Oleksandr Katilov; Valeriy Pokhylko; Leonid Dubey; Edita Poluziorovienė; Nina Prokopčiuk; Vaida Taminskienė; Arūnas Valiulis Journal: Acta Med Litu Date: 2021-02-08