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These results support that rare non-synonymous variants within these genes can alter susceptibility to human body mass index extremes.Â«Â lessĬommon variants at 12 q15 and 12 q24 are associated with infant head circumference. Functional analysismoreÂ Â» of the obese variants revealed NPY2R D42G to have reduced cell surface expression, while previous cell culture based studies indicated variant PYY Q 62 P to have altered receptor binding selectivity and we show that it fails to reduce food intake through mouse peptide injection experiments.

In total we found eleven rare non-synonymous variants, four of which exhibited familial segregation, NPY1R L53 P and PPY P63L with leanness and NPY2R D42G and PYY Q 62 P with obesity. To investigate whether nucleotide changes in these candidate genes result in abnormal weight in humans, we sequenced the coding exons and splice sites of seven family members (NPY, PYY, PPY, NPY1R, NPY2R, NPY4R, and NPY5R) in a large cohort of extremely obese (n=379) and lean (n=378) individuals.

Members of the pancreatic polypeptide family and the irreceptors have been implicated in the control of food intake in rodents and humans. A PYY Q 62 P variant linked to human obesityĭOE Office of Scientific and Technical Information (OSTI.GOV)Īhituv, Nadav Kavaslar, Nihan Schackwitz, Wendy

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