Mechanisms of asthma and allergic inflammationGenome screen for asthma and bronchial hyperresponsiveness: Interactions with passive smoke exposure
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.
References (40)
- et al.
A genome-wide search for linkage to asthma German Asthma Genetics Group
Genomics
(1999) - et al.
A second-generation genomewide screen for asthma susceptibility alleles in a founder population
Am J Hum Genet
(2000) - et al.
Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three U.S. populations: Collaborative Study on the Genetics of Asthma
Am J Hum Genet
(2001) - et al.
A major susceptibility gene for asthma maps to chromosome 14q24
Am J Hum Genet
(2002) - et al.
Major genes regulating total serum immunoglobulin E levels in families with asthma
Am J Hum Genet
(2000) - et al.
Genome-wide search for atopy susceptibility genes in Dutch families with asthma
J Allergy Clin Immunol
(2002) - et al.
Gene-gene interaction in asthma: IL4RA and IL 13 in a Dutch population
Am J Hum Genet
(2002) - et al.
Fine mapping of an IgE-controlling gene on chromosome 2q: analysis of CTLA4 and CD28
J Allergy Clin Immunol
(2002) - et al.
Relationships of bronchial responsiveness assessed by methacholine to serum IgE, lung function, symptoms, and diagnoses in 11-year-old New Zealand children
J Allergy Clin Immunol
(1992) - et al.
Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure
J Allergy Clin Immunol
(2003)
Evidence for a locus regulating total serum IgE levels mapping to chromosome 5
Genomics
Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12B locus by a genome-wide search in Japanese families
Genomics
A genome-wide search for quantitative loci underlying asthma
Nature
Genome-wide search for asthma susceptibility loci in a founder population
Hum Mol Genet
Genome screen for asthma and related phenotype in the French EGEA study
Am J Respir Crit Care Med
A genowide search for quantitative-trait loci underlying asthma
Am J Hum Genet
A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population
Nat Genet
Association of a promoter polymorphism of the CD14 gene and atopy
Am J Respir Crit Care Med
Identification and association of polymorphisms in the interleukin 13 gene with asthma and atopy in a Dutch population
Am J Respir Cell Mol Biol
Predictive nature of bronchial responsiveness and respiratory symptoms in a one year cohort study of Sydney school children
Eur Respir J
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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.