| Polymorphisms in beta-adrenergic receptor genes in the acquired long QT syndrome. | |
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MedLine Citation:
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PMID: 11942593 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Sympathetic activation is a trigger for life-threatening arrhythmias in many patients with the congenital long QT syndrome (LQTS), and an increase in heart rate has been reported just prior to torsades de pointes in patients with drug-associated (acquired) LQTS (aLQTS). We compared the frequencies of five recognized nonsynonymous coding region polymorphisms in genes encoding the beta1-adrenergic and beta2-adrenergic receptors (AR) in 93 patients with aLQTS and 3 control groups: an ethically diverse set of individuals from middle Tennessee (n = 71), a subset of the Polymorphism Discovery Resource obtained from National Human Genome Research Institute (n = 89), and patients who tolerated QT-prolonging drugs without aLQTS (non-aLQTS group; n = 66). METHODS AND RESULTS: Polymerase chain reaction-restriction fragment length polymorphism was used to screen for Ser49Gly and Gly389Arg (beta1-AR) and Thr164Ile (beta2-AR). For Arg16Gly and Gln27Glu, polymorphic sites 33 nucleotides apart in the beta2-AR, single-stranded conformational polymorphism was used to distinguish among the 4 possible haplotypes and 10 possible genotypes. Allele frequencies were similar among the 4 groups at the 2 beta1-AR sites. The uncommon Ile164 variant in beta2-AR was slightly more frequent in patients (3.2%) than in any of the 3 control groups (0.6% to 2.3%). At the 16-27 neighboring sites in the beta2-AR, one haplotype (Arg16/Glu27) was not detected, as in previous studies; hence, only 6 genotypes were present. There were fewer Gly16/Gln27 homozygotes in the non-aLQTS group (1.5%) than in two other control groups or the aLQTS group (8.5% to 10%). CONCLUSION: None of the five common nonsynonymous coding region polymorphisms in the beta-AR genes predict drug-associated torsades de pointes, although the Gly16/Gln27 haplotype may be a risk factor. |
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Authors:
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Hideaki Kanki; Ping Yang; Hong-Guang Xie; Richard B Kim; Alfred L George; Dan M Roden |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of cardiovascular electrophysiology Volume: 13 ISSN: 1045-3873 ISO Abbreviation: J. Cardiovasc. Electrophysiol. Publication Date: 2002 Mar |
Date Detail:
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Created Date: 2002-04-10 Completed Date: 2002-09-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9010756 Medline TA: J Cardiovasc Electrophysiol Country: United States |
Other Details:
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Languages: eng Pagination: 252-6 Citation Subset: IM |
Affiliation:
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Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Female Gene Frequency Haplotypes Humans Long QT Syndrome / chemically induced, genetics*, physiopathology Male Middle Aged Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational Receptors, Adrenergic, beta-1 / genetics* Receptors, Adrenergic, beta-2 / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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GM31304/GM/NIGMS NIH HHS; HL46681/HL/NHLBI NIH HHS; HL65962/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2 |
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