Asthma, allergy, and airway hyperresponsiveness are not linked to the β₂-adrenoceptor gene

Study objectives: To exclude genetic linkage between the β₂-adrenoceptor gene and asthma, allergy, and methacholine airway hyperresponsiveness. Design: The current study used six distinct intragene markers within the β₂-adrenoceptor gene, and evaluated genetic linkage between the β₂-adrenoceptor and asthma, allergy, or methacholine airway hyperresponsiveness in eight multiplex families. Patients: Forty-nine members of eight multiplex families with a high incidence of asthma. Interventions: 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 β₂-adrenoceptor gene. Measurements and results: Nonparametric analysis using computer analysis software found no evidence for linkage between these markers within the β₂-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 β₂-adrenoceptor gene with strong effect in these eight families with an inherited pattern of asthma.