| Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic-receptor gene. | |
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MedLine Citation:
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PMID: 7609750 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The beta 3-adrenergic receptor is expressed in visceral adipose tissue and is thought to contribute to the regulation of the resting metabolic rate and lipolysis. METHODS: To investigate whether mutations in the gene for the beta 3-adrenergic receptor predispose patients to obesity and non-insulin-dependent diabetes mellitus (NIDDM), we studied this gene in 10 Pima Indians by analysis of single-stranded conformational polymorphisms and dideoxy sequence analysis. Association studies were performed in 642 Pima subjects (390 with NIDDM and 252 without NIDDM). RESULTS: A missense mutation was identified in the gene for the beta 3-adrenergic receptor that results in the replacement of tryptophan by arginine (Trp64Arg) in the first intracellular loop of the receptor. This mutation was detected with allelic frequencies of 0.31 in Pima Indians, 0.13 in 62 Mexican Americans, 0.12 in 49 blacks, and 0.08 in 48 whites in the United States. Among Pimas, the frequency of the Trp64Arg mutation was similar in nondiabetic and diabetic subjects. However, in subjects homozygous for the mutation the mean (+/- SD) age at the onset of NIDDM was significantly lower (36 +/- 10 years) than in Trp64Arg heterozygotes (40 +/- 10 years) or normal homozygotes (41 +/- 11 years; P = 0.02). Furthermore, subjects with the mutation tended to have a lower adjusted resting metabolic rate (P = 0.14 by analysis of covariance). CONCLUSIONS: Pima subjects homozygous for the Trp64Arg beta 3-adrenergic-receptor mutation have an earlier onset of NIDDM and tend to have a lower resting metabolic rate. This mutation may accelerate the onset of NIDDM by altering the balance of energy metabolism in visceral adipose tissue. |
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Authors:
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J Walston; K Silver; C Bogardus; W C Knowler; F S Celi; S Austin; B Manning; A D Strosberg; M P Stern; N Raben |
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: The New England journal of medicine Volume: 333 ISSN: 0028-4793 ISO Abbreviation: N. Engl. J. Med. Publication Date: 1995 Aug |
Date Detail:
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Created Date: 1995-08-17 Completed Date: 1995-08-17 Revised Date: 2010-03-24 |
Medline Journal Info:
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Nlm Unique ID: 0255562 Medline TA: N Engl J Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 343-7 Citation Subset: AIM; IM |
Affiliation:
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Division of Geriatric Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Age of Onset Aged Basal Metabolism Base Sequence DNA Mutational Analysis Diabetes Mellitus, Type 2 / ethnology, genetics*, metabolism Gene Frequency Genotype Humans Indians, North American / genetics* Middle Aged Molecular Sequence Data Obesity / genetics Point Mutation* Polymorphism, Single-Stranded Conformational Receptors, Adrenergic, beta / genetics* Receptors, Adrenergic, beta-3 United States / epidemiology |
| Grant Support | |
ID/Acronym/Agency:
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5T32AG00120/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Adrenergic, beta; 0/Receptors, Adrenergic, beta-3 |
| Comments/Corrections | |
Comment In:
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N Engl J Med. 1995 Aug 10;333(6):382-3
[PMID:
7609759
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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