The glutamine 27 β2-adrenoceptor polymorphism is associated with elevated IgE levels in asthmatic families☆,☆☆,★,★★
Section snippets
Subjects
Three hundred twenty-four individuals from 60 unrelated families selected by means of an asthmatic proband were studied. Of these 60 families, 44 were nuclear in structure. The families were outbred, and all subjects were Caucasian. The probands were recruited from hospital clinics in the Wessex area of Southern England, and all had a physician's diagnosis of asthma. The study was approved by the Southampton University Hospitals Joint Ethical Committee. Informed written consent was obtained
Results
We used ASO hybridization7, 16 to determine the genotype of our subjects (see Methods for details). First, genomic DNA was extracted from whole blood, and a 234 base pair fragment spanning the two polymorphisms was generated by using the PCR. Genotype was then determined with probes specific for each polymorphism. Fig. 1 shows a representative ASO result on samples from 15 individuals who had previously been genotyped by direct sequencing.
In this sample of families multiplex for asthma, the
Discussion
The main findings of this study are (1) that the Gln 27 β2 adrenoceptor polymorphism is significantly associated with elevated levels of serum IgE and (2) that neither the Arg-Gly 16 nor the Gln-Glu 27 β2 adrenoceptor polymorphism was associated with an increased risk of asthma or atopy in the families studied. The potential contribution of the amino acid 27 polymorphism to IgE variability in this population was further supported by linkage analysis.
An association between total serum IgE and
References (27)
- et al.
Association of the Glu 27 β2 adrenoceptor polymorphism with lower airway reactivity in asthmatic subjects
Lancet
(1995) - et al.
Reduced responsiveness of adenylate cyclase in alveolar macrophages from patients with asthma
J Allergy Clin Immunol
(1991) - et al.
Genetic analysis of allergic disease in twins
J Allergy Clin Immunol
(1984) - et al.
cDNA for the human β2 adrenoceptor receptor: a protein with multiple membrane spanning domains and encoded by a gene whose chromosomal location is shared by the receptor for platelet-derived growth factor
Proc Natl Acad Sci USA
(1987) - et al.
Mutations in the gene coding for the β2 adrenergic receptor in normal and asthmatic subjects
Am J Respir Cell Mol Biol
(1993) - et al.
Amino-terminal polymorphisms of the human β2 adrenergic receptor impart distinct agonist-promoted regulatory properties
Biochemistry
(1994) - et al.
Influence of β2 adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells
Am J Respir Cell Mol Biol
(1995) - et al.
Genetic polymorphisms of the β2 adrenergic receptor in nocturnal and non-nocturnal asthma: evidence that Gly 16 correlates with the nocturnal phenotype
J Clin Invest
(1995) - et al.
Evidence for β2 adrenergic receptor (ADRβ2) polymorphism at amino acid 16 as a risk factor for bronchial hyperresponsiveness (BHR) [abstract]
Am J Respir Crit Care Med
(1995) The beta-adrenergic theory of the atopic abnormality in asthma
J Allergy
(1968)
Alterations in cAMP metabolism in bronchial asthma
J Clin Invest
β-Adrenergic receptor binding in lymphocytes from patients with asthma
Lung
In vitro responsiveness of human asthmatic bronchus to carbachol, histamine, βadrenoceptor agonists and theophylline
Br J Clin Pharmacol
Cited by (0)
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From athe Department of Therapeutics, University Hospital, Nottingham; bthe Departments of Medicine and Cancer Research Campaign Genetic Epidemiology Research Group, Princess Anne Hospital, Southampton; and cPulmonary and Critical Care Medicine, University of Cincinnati.
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Supported by the National Asthma Campaign, the National Institutes of Health (USA), and the Medical Research Council.
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Reprint requests: I. P. Hall, DM, National Asthma Campaign, University Hospital, Nottingham, NG7 2UH, United Kingdom.
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