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. 2005 Aug 15;172(4):446-52.
doi: 10.1164/rccm.200407-864OC. Epub 2005 May 18.

Genomewide screen for pulmonary function in 200 families ascertained for asthma

Dirkje S Postma  1 , Deborah A Meyers, Hajo Jongepier, Timothy D Howard, Gerard H Koppelman, Eugene R Bleecker
Affiliations

Genomewide screen for pulmonary function in 200 families ascertained for asthma

Dirkje S Postma et al. Am J Respir Crit Care Med. .

Abstract

Changes in pulmonary function are important in determining asthma outcome. Genetic factors may influence airway obstruction in asthma. We performed a genomewide screen in 200 families of probands objectively diagnosed with asthma in the 1960s to identify chromosomal regions related to changes in pre- and postbronchodilator lung function (FEV1, VC, and FEV1%VC) and assess influences of early-life smoke exposure. Smoking (pack-years), age, sex, and height were covariates in variance component analyses. Significant evidence for linkage of pre- and postbronchodilator FEV1%VC was obtained for chromosome 2q32 (LOD,4.9, increasing to 6.03 with additional fine-mapping markers, and 3.2, respectively). Linkage existed for chromosome 5q for pre- and postbronchodilator VC (likelihood of disease [LOD], 1.8 and 2.6, respectively). Results for pre- and postbronchodilator FEV1 were less significant (LOD, 1.5 and 1.6, chromosomes 11p and 10q, respectively). Results were not affected by passive smoke exposure. There is significant evidence for linkage of FEV1%VC to chromosome 2q32 in families of probands with asthma, 35 cM proximal from linkage previously observed in families of probands with early-onset chronic obstructive pulmonary disease. Thus, there may be multiple genes on chromosome 2q that are important in determining presence and degree of airflow limitation in families ascertained for obstructive airway disease.

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Figures

<b>Figure 1.</b>
Figure 1.
Genomewide screen for major genes regulating pre- and postbronchodilator FEV1 and VC values in 200 Dutch families from a proband with asthma. (A) Prebronchodilator FEV1; (B) postbronchodilator FEV1; (C) prebronchodilator VC; (D) postbronchodilator VC.
<b>Figure 1.</b>
Figure 1.
Genomewide screen for major genes regulating pre- and postbronchodilator FEV1 and VC values in 200 Dutch families from a proband with asthma. (A) Prebronchodilator FEV1; (B) postbronchodilator FEV1; (C) prebronchodilator VC; (D) postbronchodilator VC.
<b>Figure 1.</b>
Figure 1.
Genomewide screen for major genes regulating pre- and postbronchodilator FEV1 and VC values in 200 Dutch families from a proband with asthma. (A) Prebronchodilator FEV1; (B) postbronchodilator FEV1; (C) prebronchodilator VC; (D) postbronchodilator VC.
<b>Figure 1.</b>
Figure 1.
Genomewide screen for major genes regulating pre- and postbronchodilator FEV1 and VC values in 200 Dutch families from a proband with asthma. (A) Prebronchodilator FEV1; (B) postbronchodilator FEV1; (C) prebronchodilator VC; (D) postbronchodilator VC.
<b>Figure 2.</b>
Figure 2.
Genomewide screen for major genes regulating pre- and postbronchodilator FEV1%VC values in 200 Dutch families from a proband with asthma. No differences in y-axis scale for pre- and postbronchodilator FEV1%VC. (A) Prebronchodilator FEV1%VC; (B) postbronchodilator FEV1%VC.
<b>Figure 2.</b>
Figure 2.
Genomewide screen for major genes regulating pre- and postbronchodilator FEV1%VC values in 200 Dutch families from a proband with asthma. No differences in y-axis scale for pre- and postbronchodilator FEV1%VC. (A) Prebronchodilator FEV1%VC; (B) postbronchodilator FEV1%VC.
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References

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