Journal Article

A <i>PYY</i> Q62P variant linked to human obesity

Nadav Ahituv, Nihan Kavaslar, Wendy Schackwitz, Anna Ustaszewska, John Michael Collier, Sybil Hébert, Heather Doelle, Robert Dent, Len A. Pennacchio and Ruth McPherson

in Human Molecular Genetics

Volume 15, issue 3, pages 387-391
Published in print February 2006 | ISSN: 0964-6906
Published online December 2005 | e-ISSN: 1460-2083 | DOI:
A PYY Q62P variant linked to human obesity

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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.

Journal Article.  3372 words.  Illustrated.

Subjects: Genetics and Genomics

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