Mechanisms of asthma and allergic inflammation
Genome screen for asthma and bronchial hyperresponsiveness: Interactions with passive smoke exposure

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Background

Asthma is a common respiratory disease caused by the interaction of genetic susceptibility and exposure to various environmental factors. Passive smoke exposure, characterized by parental smoking, has been shown to be a risk factor for the development of atopy and asthma.

Objective

We sought to perform a genome-wide linkage screen for asthma and bronchial hyperresponsiveness (BHR) and to determine the influence of passive tobacco smoke exposure during childhood on the results of genetic linkage studies to investigate gene-environment interactions.

Methods

A genome-wide linkage screen for asthma and BHR was performed in 200 families ascertained through a parent with asthma. Analyses were performed separately for the entire sample and for the smoking-exposed and nonexposed families.

Results

For asthma and BHR, the strongest evidence for linkage was observed for chromosomes 3p and 5q. The families in which the children were exposed to passive smoking accounted for the evidence for linkage of BHR to 5q (P < .001), but evidence for linkage to 3p was found in both sets of families. Similar results were observed for asthma. However, there was no observed difference in the frequency of asthma or BHR in the offspring from the smoke-exposed compared with the nonexposed families.

Conclusion

The results from this study demonstrate that the influence of susceptibility genes for a common disease such as asthma might not be apparent unless there is the appropriate exposure to environmental stimuli, such as passive exposure to cigarette smoke. This approach should be useful for identification of asthma susceptibility genes.

Section snippets

Family ascertainment

Two hundred families were ascertained through probands who were initially studied between 1962 and 1975 at Beatrixoord Hospital, Haren, the Netherlands, a regional airways disease referral center. Patients with newly diagnosed symptomatic asthma who were not experiencing a current asthma exacerbation were referred to this hospital and admitted for a standardized and comprehensive evaluation for asthma and atopy. At the time of initial testing, all probands had asthma symptoms, were

Demographics

The characteristics of the family members have been described previously.10 Fig 1 shows the results of the asthma classification of the first- and second-degree offspring (n = 540) for the 200 families. Class 1 (definite asthma) was found in 21% of the offspring, whereas class 2 (probable asthma) was found in 10%, resulting in 31% of the offspring with findings consistent with a diagnosis of asthma, even though these 200 families were not ascertained for multiple family members with asthma. Class

Discussion

This study reports the results of linkage analysis for asthma and bronchial responsiveness by using a well-characterized, homogeneous asthmatic family population. The families were not ascertained through multiple affected siblings but through a single proband (a parent) with asthma, and analysis of the offspring showed a high frequency of asthma phenotypes (31% with asthma or probable asthma [classes 1 and 2] and 46% with BHR), supporting an important hereditary component for these phenotypes.

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    Supported by the Dutch Asthma Funds grant AF 95.09 and National Institutes of Health (NIH) grants R01HL/48341 and R01HL/66393.

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