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Human Obesity Associated with an Intronic SNP in the Brain-Derived Neurotrophic Factor Locus.
Mou, Zongyang; Hyde, Thomas M; Lipska, Barbara K; Martinowich, Keri; Wei, Peter; Ong, Chiew-Jen; Hunter, Lindsay A; Palaguachi, Gladys I; Morgun, Eva; Teng, Rujia; Lai, Chen; Condarco, Tania A; Demidowich, Andrew P; Krause, Amanda J; Marshall, Leslie J; Haack, Karin; Voruganti, V Saroja; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G; Nalls, Michael A; Zonderman, Alan B; Singleton, Andrew B; Evans, Michele K; Martin, Bronwen; Maudsley, Stuart; Tsao, Jack W; Kleinman, Joel E; Yanovski, Jack A; Han, Joan C.
Afiliação
  • Mou Z; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD
  • Hyde TM; The Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medi
  • Lipska BK; Human Brain Collection Core, National Institute of Mental Health (NIMH), NIH, Bethesda, MD 20892, USA.
  • Martinowich K; The Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Wei P; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Departments of Neurology and Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, MD 2081
  • Ong CJ; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Departments of Neurology and Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, MD 2081
  • Hunter LA; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Departments of Neurology and Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, MD 2081
  • Palaguachi GI; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Departments of Neurology and Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, MD 2081
  • Morgun E; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD
  • Teng R; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA.
  • Lai C; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Departments of Neurology and Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, MD 2081
  • Condarco TA; Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA.
  • Demidowich AP; Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA.
  • Krause AJ; Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA.
  • Marshall LJ; Preclinical Microbicide & Prevention Research Branch, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Haack K; Department of Genetics, Texas Biomedical Research Institute and Southwest National Primate Research Center, San Antonio, TX 78245, USA.
  • Voruganti VS; Department of Genetics, Texas Biomedical Research Institute and Southwest National Primate Research Center, San Antonio, TX 78245, USA; Department of Nutrition and UNC Nutrition Research Institute, University of North Carolina, Chapel Hill, Kannapolis, NC 28081, USA.
  • Cole SA; Department of Genetics, Texas Biomedical Research Institute and Southwest National Primate Research Center, San Antonio, TX 78245, USA.
  • Butte NF; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Comuzzie AG; Department of Genetics, Texas Biomedical Research Institute and Southwest National Primate Research Center, San Antonio, TX 78245, USA.
  • Nalls MA; Molecular Genetics Section, National Institute of Aging (NIA), Bethesda, MD 20892, USA.
  • Zonderman AB; Behavioral Epidemiology Section, NIA, Baltimore, MD 21224, USA.
  • Singleton AB; Molecular Genetics Section, National Institute of Aging (NIA), Bethesda, MD 20892, USA.
  • Evans MK; Health Disparities Research Section, NIA, Baltimore, MD 21224, USA.
  • Martin B; Metabolism Unit, NIA, Baltimore, MD 21224, USA.
  • Maudsley S; Receptor Pharmacology Unit, NIA, Baltimore, MD 21224, USA; Translational Neurobiology Group, VIB Department of Molecular Genetics, University of Antwerp, 2610 Wilrijk, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, 2610 Wilrijk, Belgium.
  • Tsao JW; Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Departments of Neurology and Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Depa
  • Kleinman JE; The Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medi
  • Yanovski JA; Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA.
  • Han JC; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, USA; Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD
Cell Rep ; 13(6): 1073-1080, 2015 Nov 10.
Article em En | MEDLINE | ID: mdl-26526993
ABSTRACT
Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 BDNF SNPs. We observed that the minor C allele of rs12291063 is associated with lower human ventromedial hypothalamic BDNF expression (p < 0.001) and greater adiposity in both adult and pediatric cohorts (p values < 0.05). We further demonstrated that the major T allele for rs12291063 possesses a binding capacity for the transcriptional regulator, heterogeneous nuclear ribonucleoprotein D0B, knockdown of which disrupts transactivation by the T allele. Binding and transactivation functions are both disrupted by substituting C for T. These findings provide a rationale for BDNF augmentation as a targeted treatment for obesity in individuals who have the rs12291063 CC genotype.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator Neurotrófico Derivado do Encéfalo / Polimorfismo de Nucleotídeo Único / Obesidade Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Rep Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Moldávia
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator Neurotrófico Derivado do Encéfalo / Polimorfismo de Nucleotídeo Único / Obesidade Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Rep Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Moldávia