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• W2157226274 startingPage "334" @default.
• W2157226274 abstract "It has long been hypothesized that a defective β2-adrenergic receptor (β2AR) may be a pathogenic factor in bronchial asthma. We examined the gene encoding the β2AR to assess the frequency of polymorphisms in 51 patients with moderate to severe asthma and 56 normal subjects. Nine different point mutations were found in both heterozygous and homozygous forms at nucleic acid residues 46, 79, 100, 252, 491, 523, 1053, 1098, and 1239. No mutations resulting in large deletions or frame shifts were detected. Of these nine polymorphisms, four were found to cause changes in the encoded amino acids at residues 16, 27, 34, and 164. The most frequent polymorphisms were arginine 16 to glycine (Arg16→Gly) and glutamine 27 to glutamic acid (Gln27→Glu). The other two polymorphisms, valine 34 to methionine, and threonine 164 to isoleucine, occurred in only four subjects. The incidence of β2AR homozygous polymorphisms was no greater in asthmatic patients as compared with controls (Arg16→Gly: 53% versus 59%, Gln27→Glu: 24% versus 29%, respectively; P = NS). Some subjects were found to have both of these polymorphisms simultaneously, but there was no difference in incidence between the two groups, with 23% of asthmatics and 28% of normal subjects being homozygous for both polymorphisms. The apparently normal subjects with both polymorphisms did not have subclinical hyperreactive airways disease as determined by methacholine challenge testing. In the asthma group, one mutation (Arg16→Gly) identified a subset of patients with a distinct clinical profile. Patients with this polymorphism were more likely to be steroid dependent and to require immunization therapy, as compared with those without this polymorphism. Other parameters of asthma severity or medication use were not related to the presence of a polymorphism at any locus. Thus, asthma does not appear to be primarily caused by a genetic defect in the β2AR. However, the Arg16→Gly polymorphism may be associated with a different clinical status, suggesting that an alteration in the gene encoding for the β2AR plays an accessory role in the pathogenesis of asthma in certain patients." @default.
• W2157226274 created "2016-06-24" @default.
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• W2157226274 date "1993-03-01" @default.
• W2157226274 modified "2023-10-15" @default.
• W2157226274 title "Mutations in the Gene Encoding for the <i>β</i>₂-adrenergic Receptor in Normal and Asthmatic Subjects" @default.
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• W2157226274 doi "https://doi.org/10.1165/ajrcmb/8.3.334" @default.
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