| A PYY Q62P variant linked to human obesity. | |
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MedLine Citation:
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PMID: 16368708 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Peptide YY (PYY) has been implicated in the control of food intake through functional studies in rodents and humans. To investigate whether genetic alterations within this gene result in abnormal weight in humans, we sequenced its coding exons and splice sites in a large cohort of extremely obese [n = 379; average body mass index (BMI), 49.0 kg/m2] and lean (n = 378; average BMI, 19.5 kg/m2) individuals. In total, three rare non-synonymous variants were identified, only one of which, PYY Q62P, exhibited familial segregation with body mass. Through serendipity, previous studies based on cell culture revealed this precise variant to have altered receptor-binding selectivity in vitro. We further show, using mouse peptide injection experiments, that while the wild-type PYY peptide reduces food intake, the mutant PYY 62P had an insignificant effect in reducing food intake in vivo. Taken together, these results are the first to support that rare sequence variants within PYY can influence human susceptibility to obesity. |
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Authors:
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Nadav Ahituv; Nihan Kavaslar; Wendy Schackwitz; Anna Ustaszewska; John Michael Collier; Sybil Hébert; Heather Doelle; Robert Dent; Len A Pennacchio; Ruth McPherson |
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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, Non-P.H.S. Date: 2005-12-20 |
Journal Detail:
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Title: Human molecular genetics Volume: 15 ISSN: 0964-6906 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-19 Completed Date: 2006-04-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: England |
Other Details:
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Languages: eng Pagination: 387-91 Citation Subset: IM |
Affiliation:
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Genomics Division, One Cyclotron Road, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Case-Control Studies Eating / physiology Fasting / metabolism Genetic Predisposition to Disease Humans Male Mice Molecular Sequence Data Mutation, Missense / genetics* Obesity / genetics* Pedigree Peptide YY / genetics* Postprandial Period Sequence Alignment Sequence Analysis, DNA |
| Chemical | |
Reg. No./Substance:
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106388-42-5/Peptide YY |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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