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Cited by 269

The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.

Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression.

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McGraw, D W, Forbes, S L, Kramer, L A, Liggett, S B·1998·Journal of Clinical Investigation

Abstract

Cellular expression of the beta2-adrenergic receptor (beta2AR) is controlled in part by a 19-amino acid peptide that regulates mRNA translation. This peptide is encoded by a short open reading frame, termed the 5' leader cistron (5'LC), which is 102 bp upstream of the beta2AR coding block. In 176 normal subjects we found a single nucleotide polymorphism resulting in either Arg (previously denoted wild-type) or Cys at position 19 of this peptide. Allele frequencies were 0.37 for Arg and 0.63 for Cys. To determine if these variants altered beta2AR expression, COS-7 cells were transfected with polymorphic constructs consisting of 1,989 bp encompassing the 5'LC and the beta2AR coding block exactly as found in the human gene. beta2AR density, as determined by [125I]CYP radioligand binding, was 72% higher in cells transfected with the 5'LC-Cys19 construct as compared with those transfected with the 5'LC-Arg19 construct and 110% higher when a cotransfection technique with a luciferase construct was used to control for transfection efficiency. Levels of the two mRNA transcripts were not different, confirming in vitro studies that the upstream peptide regulates receptor expression at the translational level. In human airway smooth muscle cells that natively express beta2AR, receptor expression was approximately twofold higher in those bearing the Cys versus the Arg polymorphism, confirming the phenotype in a relevant cell type. Linkage disequilibrium was observed between the 5'LC-Cys polymorphism and the beta2AR coding block polymorphisms Arg16 and Gln27 (P < 0.0001), although several different haplotypes were identified. Thus, beta2AR expression in the human population is controlled by a common polymorphism of this 5'LC, and may be responsible for interindividual variation in betaAR responsiveness.

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Metadata

Authors
McGraw, D. W., Forbes, S. L., Kramer, L. A., & Liggett, S. B.
Venue
Journal of Clinical Investigation
Published
1998-12-01
Volume
102
Issue
11
Pages
1927-1932
ISSN
0021-9738 (ISSN-L)
OpenAlex
W1992530497
Cited by
269
References
23
FWCI
5.85
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression. https://app.cochat.ai/papers/10.1172/jci4862
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McGraw, D. W., Forbes, S. L., Kramer, L. A., & Liggett, S. B. (1998). Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression. Journal of Clinical Investigation. https://doi.org/10.1172/jci4862

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