Abstract MP75: Assessment of the Genetic Role of Potential Metabolic Therapeutic Targets Along Insulin Signaling and Adipogenesis Pathways

Recent studies in rat hepatoma cells identified MAP kinase phosphatase 3 (MKP3) as the key player in antagonizing repression of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription by insulin, indicating that MAP kinase phosphatase can crosstalk with metabolic components of the insulin signaling pathways. The family of histone deacetylases (HDACs) is another set of metabolic therapeutic targets of importance as HDAC1 has recently been shown to be involved in regulating preadipocyte differentiation. We therefore investigated the roles of MKP3 (DUSP6 in human), PEPCK (PCK2), HDAC1u00262 single nucleotide polymorphisms (SNPs) in relation to obesity and diabetes risk among 7,287 African American (AA), 3,258 Hispanic American (HA), and 3711 Caucasian American (CA) women participating in the national Women’s Health Initiative (WHI) SNP Health Association Resource (SHARe) and the Genomics and Randomized Trials Network (GARNET). We found significant association between 43 SNPs in the DUSP6 gene region with ri...