TY - JOUR T1 - Risk for asthma exacerbations in association with variations in the genes coding for the glutathione S-transferase family JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA3132 VL - 48 IS - suppl 60 SP - PA3132 AU - Stephen Turner AU - Ben Francis AU - Susanne Vijverberg AU - Maria Pino-Yanes AU - Annke-Hilse Maitland-van der Zee AU - Roger Tavendale AU - Esteban Burchard AU - Somnath Mukhopadhyay AU - Colin Palmer Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA3132.abstract N2 - Introduction: Asthma is associated with increased oxidant stress which is further escalated during an exacerbation. Glutathione S-transferases (GST) have protective role against oxidative stress in the airway. Our hypothesis was that children with functional genetic variants at GSTP1, GSTM1, and GSTP1 are at increased risk for exacerbation compared to children not carrying these variants.Methods: Children with asthma were recruited and genotyped in four populations (BREATHE, GALA II, PACMAN and PAGES). The rs1695 single nucleotide polymorphism (Ile105Val missense variant of the GSTP1 gene) and GSTM1 and GSTT1 null variants were determined. A history of exacerbation was recorded.Results: All GST genetic variations were available in 2197 participants from BREATHE, PACMAN and PAGES, and GSTP1 data alone were available from 1330 GALA II participants. The odds ratio (OR) for children with the GSTT1 null variant having an exacerbation were increased compared to wild type (1.32 [95% CI 1.02, 1.71] p=0.033) but not for GSTM1 null or homozygous Val genotype compared to other genotypes. There was no evidence of an additive GST variant effect on OR for exacerbation. The OR for exacerbation among GSTT1 null children who were exposed to second hand smoke (SHS) was 1.69 [1.02, 2.73] p=0.042 compared to GSTT1 wild type children who were exposed. The OR for exacerbation was no different between children who were GSTT1 null and GSTT1 wild type who were not exposed to SHS.Conclusion: The GSTT1 null mutation is associated with a modest increase in risk for exacerbation in children with asthma. The risk appears to be modified by environmental factors, e.g. exposure to SHS. ER -