Genetic susceptibility to asthma - Bronchial hyperresponsiveness coinherited with a major gene for atopy

D. S. Postma, E. R. Bleecker, P. J. Amelung, K. J. Holroyd, J. Xu, C. I M Panhuysen, D. A. Meyers, Roy C Levitt

Research output: Contribution to journalArticle

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Abstract

Background. Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma. Methods. We studied 303 children and grandchildren of 84 probands with asthma selected from a homogeneous population in the Netherlands. Ventilatory function, bronchial responsiveness to histamine, and serum total IgE were measured. The association between the last two variables was evaluated. Using analyses involving pairs of siblings, we tested for linkage between bronchial hyperresponsiveness and genetic markers on chromosome 5q31-q33, previously shown to be linked to a genetic locus regulating serum total IgE levels. Results. Serum total IgE levels were strongly correlated (r=0.65, P<0.01) in pairs of siblings concordant for bronchial hyperresponsiveness (defined as a ≥20 percent decrease in the forced expiratory volume in one second produced by histamine [threshold dose, ≤16 mg per milliliter]), suggesting that these traits are coinherited. However, bronchial hyperresponsiveness was not correlated with serum IgE levels (r=0.04, P>0.10). Analyses of pairs of siblings showed linkage of bronchial hyperresponsiveness with several genetic markers on chromosome 5q, including D5S436 (P<0.001 for a histamine threshold value of ≤16 mg per milliliter). Conclusions. This study demonstrates that a trait for an elevated level of serum total IgE is coinherited with a trait for bronchial hyperresponsiveness and that a gene governing bronchial hyperresponsiveness is located near a major locus that regulates serum IgE levels on chromosome 5q. These findings are consistent with the existence of one or more genes on chromosome 5q31-q33 causing susceptibility to asthma.

Original languageEnglish
Pages (from-to)894-900
Number of pages7
JournalNew England Journal of Medicine
Volume333
Issue number14
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Genetic Predisposition to Disease
Immunoglobulin E
Asthma
Chromosomes
Serum
Genes
Genetic Markers
Histamine
Siblings
Bronchoconstrictor Agents
Genetic Loci
Netherlands
Inflammation
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Genetic susceptibility to asthma - Bronchial hyperresponsiveness coinherited with a major gene for atopy. / Postma, D. S.; Bleecker, E. R.; Amelung, P. J.; Holroyd, K. J.; Xu, J.; Panhuysen, C. I M; Meyers, D. A.; Levitt, Roy C.

In: New England Journal of Medicine, Vol. 333, No. 14, 01.01.1995, p. 894-900.

Research output: Contribution to journalArticle

Postma, DS, Bleecker, ER, Amelung, PJ, Holroyd, KJ, Xu, J, Panhuysen, CIM, Meyers, DA & Levitt, RC 1995, 'Genetic susceptibility to asthma - Bronchial hyperresponsiveness coinherited with a major gene for atopy', New England Journal of Medicine, vol. 333, no. 14, pp. 894-900. https://doi.org/10.1056/NEJM199510053331402
Postma, D. S. ; Bleecker, E. R. ; Amelung, P. J. ; Holroyd, K. J. ; Xu, J. ; Panhuysen, C. I M ; Meyers, D. A. ; Levitt, Roy C. / Genetic susceptibility to asthma - Bronchial hyperresponsiveness coinherited with a major gene for atopy. In: New England Journal of Medicine. 1995 ; Vol. 333, No. 14. pp. 894-900.
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abstract = "Background. Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma. Methods. We studied 303 children and grandchildren of 84 probands with asthma selected from a homogeneous population in the Netherlands. Ventilatory function, bronchial responsiveness to histamine, and serum total IgE were measured. The association between the last two variables was evaluated. Using analyses involving pairs of siblings, we tested for linkage between bronchial hyperresponsiveness and genetic markers on chromosome 5q31-q33, previously shown to be linked to a genetic locus regulating serum total IgE levels. Results. Serum total IgE levels were strongly correlated (r=0.65, P<0.01) in pairs of siblings concordant for bronchial hyperresponsiveness (defined as a ≥20 percent decrease in the forced expiratory volume in one second produced by histamine [threshold dose, ≤16 mg per milliliter]), suggesting that these traits are coinherited. However, bronchial hyperresponsiveness was not correlated with serum IgE levels (r=0.04, P>0.10). Analyses of pairs of siblings showed linkage of bronchial hyperresponsiveness with several genetic markers on chromosome 5q, including D5S436 (P<0.001 for a histamine threshold value of ≤16 mg per milliliter). Conclusions. This study demonstrates that a trait for an elevated level of serum total IgE is coinherited with a trait for bronchial hyperresponsiveness and that a gene governing bronchial hyperresponsiveness is located near a major locus that regulates serum IgE levels on chromosome 5q. These findings are consistent with the existence of one or more genes on chromosome 5q31-q33 causing susceptibility to asthma.",
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T1 - Genetic susceptibility to asthma - Bronchial hyperresponsiveness coinherited with a major gene for atopy

AU - Postma, D. S.

AU - Bleecker, E. R.

AU - Amelung, P. J.

AU - Holroyd, K. J.

AU - Xu, J.

AU - Panhuysen, C. I M

AU - Meyers, D. A.

AU - Levitt, Roy C

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Y1 - 1995/1/1

N2 - Background. Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma. Methods. We studied 303 children and grandchildren of 84 probands with asthma selected from a homogeneous population in the Netherlands. Ventilatory function, bronchial responsiveness to histamine, and serum total IgE were measured. The association between the last two variables was evaluated. Using analyses involving pairs of siblings, we tested for linkage between bronchial hyperresponsiveness and genetic markers on chromosome 5q31-q33, previously shown to be linked to a genetic locus regulating serum total IgE levels. Results. Serum total IgE levels were strongly correlated (r=0.65, P<0.01) in pairs of siblings concordant for bronchial hyperresponsiveness (defined as a ≥20 percent decrease in the forced expiratory volume in one second produced by histamine [threshold dose, ≤16 mg per milliliter]), suggesting that these traits are coinherited. However, bronchial hyperresponsiveness was not correlated with serum IgE levels (r=0.04, P>0.10). Analyses of pairs of siblings showed linkage of bronchial hyperresponsiveness with several genetic markers on chromosome 5q, including D5S436 (P<0.001 for a histamine threshold value of ≤16 mg per milliliter). Conclusions. This study demonstrates that a trait for an elevated level of serum total IgE is coinherited with a trait for bronchial hyperresponsiveness and that a gene governing bronchial hyperresponsiveness is located near a major locus that regulates serum IgE levels on chromosome 5q. These findings are consistent with the existence of one or more genes on chromosome 5q31-q33 causing susceptibility to asthma.

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