BACKGROUND: Gene variants on chromosome 17q12-21 are associated with an increased risk of childhood-onset asthma, a risk known to be modified by environmental tobacco smoke (ETS). OBJECTIVES: To assess whether the association of rs2305480 on chromosome 17q12 in the GSDML gene with asthma-like symptoms in the first 4 years of life is modified by smoke exposure during fetal and early postnatal life. METHODS: We used data from two independent prospective cohort studies from fetal life onwards in the Netherlands. We genotyped rs2305480 and assessed maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma-like symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal cough, were reported by parents when the children were 1, 2, 3, and 4 years. Analyses were based on a total group of 4461 Caucasian children. RESULTS: The G risk-allele of rs2305480 was associated with asthma-like symptoms [overall odds ratio 1.17 (1.11, 1.24), 2.66E-9]. The effect of rs2305480 on asthma-like symptoms was stronger among children who were exposed to smoke during fetal life (P-interaction = 0.04). Smoke exposure in early postnatal life was also associated with an increased effect of the 17q12 single nucleotide polymorphism (SNP) on asthma-like symptoms (P-interaction = 5.06E-4). These associations were consistent in both cohorts. CONCLUSION: A 17q12 variant, rs2305480, was associated with asthma-like symptoms in preschool children, and this association was modified by smoke exposure already during fetal life, and in infancy. Further investigation regarding SNPs in linkage disequilibrium with rs2305480 in relation to pathophysiological pathways is needed.
BACKGROUND: Gene variants on chromosome 17q12-21 are associated with an increased risk of childhood-onset asthma, a risk known to be modified by environmental tobacco smoke (ETS). OBJECTIVES: To assess whether the association of rs2305480 on chromosome 17q12 in the GSDML gene with asthma-like symptoms in the first 4 years of life is modified by smoke exposure during fetal and early postnatal life. METHODS: We used data from two independent prospective cohort studies from fetal life onwards in the Netherlands. We genotyped rs2305480 and assessed maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma-like symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal cough, were reported by parents when the children were 1, 2, 3, and 4 years. Analyses were based on a total group of 4461 Caucasian children. RESULTS: The G risk-allele of rs2305480 was associated with asthma-like symptoms [overall odds ratio 1.17 (1.11, 1.24), 2.66E-9]. The effect of rs2305480 on asthma-like symptoms was stronger among children who were exposed to smoke during fetal life (P-interaction = 0.04). Smoke exposure in early postnatal life was also associated with an increased effect of the 17q12 single nucleotide polymorphism (SNP) on asthma-like symptoms (P-interaction = 5.06E-4). These associations were consistent in both cohorts. CONCLUSION: A 17q12 variant, rs2305480, was associated with asthma-like symptoms in preschool children, and this association was modified by smoke exposure already during fetal life, and in infancy. Further investigation regarding SNPs in linkage disequilibrium with rs2305480 in relation to pathophysiological pathways is needed.
Authors: Claudia J Kruithof; Marjolein N Kooijman; Cornelia M van Duijn; Oscar H Franco; Johan C de Jongste; Caroline C W Klaver; Johan P Mackenbach; Henriëtte A Moll; Hein Raat; Edmond H H M Rings; Fernando Rivadeneira; Eric A P Steegers; Henning Tiemeier; Andre G Uitterlinden; Frank C Verhulst; Eppo B Wolvius; Albert Hofman; Vincent W V Jaddoe Journal: Eur J Epidemiol Date: 2014-12-21 Impact factor: 8.082
Authors: Minal Calışkan; Yury A Bochkov; Eskil Kreiner-Møller; Klaus Bønnelykke; Michelle M Stein; Gaixin Du; Hans Bisgaard; Daniel J Jackson; James E Gern; Robert F Lemanske; Dan L Nicolae; Carole Ober Journal: N Engl J Med Date: 2013-03-27 Impact factor: 91.245
Authors: Carole Ober; Chris G McKennan; Kevin M Magnaye; Matthew C Altman; Charles Washington; Catherine Stanhope; Katherine A Naughton; Mario G Rosasco; Leonard B Bacharier; Dean Billheimer; Diane R Gold; Lisa Gress; Tina Hartert; Suzanne Havstad; Gurjit K Khurana Hershey; Brian Hallmark; D Kyle Hogarth; Daniel J Jackson; Christine C Johnson; Meyer Kattan; Robert F Lemanske; Susan V Lynch; Eneida A Mendonca; Rachel L Miller; Edward T Naureckas; George T O'Connor; Christine M Seroogy; Ganesa Wegienka; Steven R White; Robert A Wood; Anne L Wright; Edward M Zoratti; Fernando D Martinez; Dennis Ownby; Dan L Nicolae; Albert M Levin; James E Gern Journal: Lancet Respir Med Date: 2020-05 Impact factor: 30.700
Authors: Maria C Magnus; Hein Stigum; Siri E Håberg; Per Nafstad; Stephanie J London; Wenche Nystad Journal: PLoS One Date: 2015-01-30 Impact factor: 3.240