Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

M. Kerkhof, H.M. Boezen, R. Granell, A.H. Wijga, B. Brunekreef, H.A. Smit, J.C. de Jongste, C. Thijs, M. Mommers, J. Penders, J. Henderson, G.H. Koppelman, D.S. Postma

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Abstract

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 withmoreTEWinPIAMAand 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 PIAMAonly, 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.
Original languageEnglish
Pages (from-to)68-76.e4
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number1
DOIs
Publication statusPublished - 1 Jan 2014

Cite this

Kerkhof, M. ; Boezen, H.M. ; Granell, R. ; Wijga, A.H. ; Brunekreef, B. ; Smit, H.A. ; de Jongste, J.C. ; Thijs, C. ; Mommers, M. ; Penders, J. ; Henderson, J. ; Koppelman, G.H. ; Postma, D.S. / Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes. In: Journal of Allergy and Clinical Immunology. 2014 ; Vol. 133, No. 1. pp. 68-76.e4.
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title = "Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes",
abstract = "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 withmoreTEWinPIAMAand 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 PIAMAonly, 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.",
author = "M. Kerkhof and H.M. Boezen and R. Granell and A.H. Wijga and B. Brunekreef and H.A. Smit and {de Jongste}, J.C. and C. Thijs and M. Mommers and J. Penders and J. Henderson and G.H. Koppelman and D.S. Postma",
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Kerkhof, M, Boezen, HM, Granell, R, Wijga, AH, Brunekreef, B, Smit, HA, de Jongste, JC, Thijs, C, Mommers, M, Penders, J, Henderson, J, Koppelman, GH & Postma, DS 2014, 'Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes', Journal of Allergy and Clinical Immunology, vol. 133, no. 1, pp. 68-76.e4. https://doi.org/10.1016/j.jaci.2013.06.004

Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes. / Kerkhof, M.; Boezen, H.M.; Granell, R.; Wijga, A.H.; Brunekreef, B.; Smit, H.A.; de Jongste, J.C.; Thijs, C.; Mommers, M.; Penders, J.; Henderson, J.; Koppelman, G.H.; Postma, D.S.

In: Journal of Allergy and Clinical Immunology, Vol. 133, No. 1, 01.01.2014, p. 68-76.e4.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

AU - Kerkhof, M.

AU - Boezen, H.M.

AU - Granell, R.

AU - Wijga, A.H.

AU - Brunekreef, B.

AU - Smit, H.A.

AU - de Jongste, J.C.

AU - Thijs, C.

AU - Mommers, M.

AU - Penders, J.

AU - Henderson, J.

AU - Koppelman, G.H.

AU - Postma, D.S.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 withmoreTEWinPIAMAand 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 PIAMAonly, 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.

AB - 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 withmoreTEWinPIAMAand 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 PIAMAonly, 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.

U2 - 10.1016/j.jaci.2013.06.004

DO - 10.1016/j.jaci.2013.06.004

M3 - Article

VL - 133

SP - 68-76.e4

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 1

ER -