Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes - 25/12/13
, H. Marike Boezen, PhD a, b, Raquel Granell, PhD c, Alet H. Wijga, PhD d, Bert Brunekreef, PhD e, f, Henriëtte A. Smit, PhD f, Johan C. de Jongste, MD, PhD g, Carel Thijs, PhD h, Monique Mommers, PhD h, John Penders, PhD h, John Henderson, MD c, Gerard H. Koppelman, MD, PhD i, Dirkje S. Postma, MD, PhD jAbstract |
Background |
It 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.
Objective |
We 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.
Methods |
The 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.
Results |
AGER 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.
Conclusion |
Our 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.
Il testo completo di questo articolo è disponibile in PDF.Key words : Chronic obstructive pulmonary disease, transient early wheeze, lung function growth, in utero exposure
Abbreviations used : ALSPAC, COPD, ETS, FVC, KOALA, OR, PIAMA, RAGE, SNP, TEW
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| ☆ | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Supported by the Dutch Asthma Foundation (grant 3.2.09.043); ZonMw (the Netherlands Organization for Health Research and Development); the Netherlands Ministry of Spatial Planning, Housing and the Environment; and the Netherlands Ministry of Health, Welfare and Sport. The UK Medical Research Council, Wellcome Trust (grant 092731), and the University of Bristol provided core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). |
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| Disclosure of potential conflict of interest: M. Kerkhof has received grants from the Dutch Asthma Foundation. C. Thijs has received grants from the Netherlands Asthma Foundation. J. Henderson has received grants from the Wellcome Trust and the Medical Research Council. G. H. Koppelman has received grants from the Netherlands Asthma Foundation and Stichting Asthma Bestrijding. D. S. Postma has consultant arrangements with AstraZeneca, Boehringer, Chiesi, Nycomed, and TEVA and has received grants from AstraZeneca and Chiesi. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 133 - N° 1
P. 68 - gennaio 2014 Ritorno al numero
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