Cell reports · 2015
Human Obesity Associated with an Intronic SNP in the Brain-Derived Neurotrophic Factor Locus.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.