• Marjan Kerkhof, H Marike Boezen, Raquel Granell, Alet H Wijga, Bert Brunekreef, Henriëtte A Smit, Johan C de Jongste, Carel Thijs, Monique Mommers, John Penders, John Henderson, Gerard H Koppelman, and Dirkje S Postma.
• Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; GRIAC Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: m.kerkhof@umcg.nl.
• J. Allergy Clin. Immunol. 2014 Jan 1;133(1):68-76.e1-4.

BackgroundIt has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in childhood.ObjectiveWe investigated whether replicated genes for COPD associate with transient early wheeze (TEW) and lung function levels in 6- to 8-year-old children and whether cigarette smoke exposure in utero and after birth (environmental tobacco smoke [ETS]) modifies these effects.MethodsThe association of COPD-related genotypes of 20 single nucleotide polymorphisms in 15 genes with TEW, FEV1, forced vital capacity (FVC), and FEV1/FVC ratio was studied in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort (n = 1996) and replicated in the Child, parents and health: lifestyle and genetic constitution (KOALA) and Avon Longitudinal Study of Parents and Children (ALSPAC) cohorts.ResultsAGER showed replicated association with FEV1/FVC ratio. TNS1 associated with more TEW in PIAMA and lower FEV1 in ALSPAC. TNS1 interacted with ETS in PIAMA, showing lower FEV1 in exposed children. HHIP rs1828591 interacted with cigarette smoke exposure in utero in PIAMA and with ETS in ALSPAC, with lower lung function in nonexposed children. SERPINE2, FAM13A, and MMP12 associated with higher FEV1 and FVC, and SERPINE2, HHIP, and TGFB1 interacted with cigarette smoke exposure in utero in PIAMA only, showing adverse effects of exposure on FEV1 being limited to children with genotypes conferring the lowest risk of COPD.ConclusionOur findings indicate relevant involvement of at least 3 COPD genes in lung development and lung growth by demonstrating associations pointing toward reduced airway caliber in early childhood. Furthermore, our results suggest that COPD genes are involved in the infant's lung response to smoke exposure in utero and in early life.Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.

43 keywords...

hide…