Published ahead of print on May 18, 2005, doi:10.1164/rccm.200407-864OC
Am. J. Respir. Crit. Care Med., Volume 172, Number 4, August 2005, 446-452
A more recent version of this article appeared on August 15, 2005
Submitted on July 6, 2004
Accepted on May 15, 2005
Genome Wide Screen for Pulmonary Function in 200 Families Ascertained for Asthma
Dirkje S Postma1*, Deborah A Meyers2, Hajo Jongepier3, Timothy D Howard2, Gerard H Koppelman4, and Eugene R Bleecker2
1 Department of Pulmonology, University Hospital Groningen, Groningen, The Netherlands,
2 Department of Pediatrics, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA,
3 Department of Pulmonology, University Hospital Groningen, Groningen, The Netherlands; Department of Pulmonary Rehabiliation, Beatrixoord, Haren, The Netherlands,
4 Beatrix Children's Hospital, University Hospital Groningen, Groningen, The Netherlands
* To whom correspondence should be addressed. E-mail: d.s.postma{at}int.azg.nl.
Changes in pulmonary function are important in determining asthma outcome. Genetic factors may influence airway obstruction in asthma.
We performed a genome-wide 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 assessed 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 (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 COPD. 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.
Key words: asthma, lung, function, linkage, genes
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