Asthma, allergy, and airway hyperresponsiveness are not linked to the beta(2)-adrenoceptor gene.
OBJECTIVE
To exclude genetic linkage between the beta(2)-adrenoceptor gene and asthma, allergy, and methacholine airway hyperresponsiveness.


METHODS
The current study used six distinct intragene markers within the beta(2)-adrenoceptor gene, and evaluated genetic linkage between the beta(2)-adrenoceptor and asthma, allergy, or methacholine airway hyperresponsiveness in eight multiplex families.


METHODS
Forty-nine members of eight multiplex families with a high incidence of asthma.


METHODS
Phenotypes were characterized by history, physical examination, skin testing, pulmonary function tests, and methacholine inhalational challenge. Genetic loci were identified using restriction fragment length polymorphisms, denaturing gradient gel electrophoresis, and restriction enzyme digest of polymerase chain reaction-amplified fragments of the beta(2)-adrenoceptor gene.


RESULTS
Nonparametric analysis using computer analysis software found no evidence for linkage between these markers within the beta(2)-adrenoceptor gene and asthma. Parametric exclusion analysis using a dominant inheritance model resulted in large negative lod scores (- 6.74, - 19.44, and - 49.9, respectively) for tight linkage between asthma, allergy, or methacholine airway hyperresponsiveness and these polymorphic markers.


CONCLUSIONS
These results indicate that asthma, allergy, and methacholine airway hyperresponsiveness are not linked to a dominant beta(2)-adrenoceptor gene with strong effect in these eight families with an inherited pattern of asthma.
Emala
Charles W
CW
Department of Anesthesiology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. cwe5@columbia.edu
McQuitty
Christopher K
CK
Eleff
Scott M
SM
Hopkins-Price
Patricia
P
Lawyer
Carl
C
Hoh
Josephine
J
Ott
Jurg
J
Levine
Michael A
MA
Hirshman
Carol A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D001985:Bronchial Provocation Tests; D002648:Child; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2