a pparα promoter variant impairs err-dependent transactivation and decreases mortality after acute coronary ischemia in patients with diabetespparα发起人变体损害err-dependent transactivation和降低死亡率后急性冠脉缺血患者的糖尿病.pdfVIP

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a pparα promoter variant impairs err-dependent transactivation and decreases mortality after acute coronary ischemia in patients with diabetespparα发起人变体损害err-dependent transactivation和降低死亡率后急性冠脉缺血患者的糖尿病.pdf

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a pparα promoter variant impairs err-dependent transactivation and decreases mortality after acute coronary ischemia in patients with diabetespparα发起人变体损害err-dependent transactivation和降低死亡率后急性冠脉缺血患者的糖尿病

A PPARa Promoter Variant Impairs ERR-Dependent Transactivation and Decreases Mortality after Acute Coronary Ischemia in Patients with Diabetes 1 2 3 4 1 Sharon Cresci *, Janice M. Huss , Amber L. Beitelshees , Philip G. Jones , Matt R. Minton , Gerald W. 1 5 4 6 Dorn II , Daniel P. Kelly , John A. Spertus , Howard L. McLeod 1 Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America, 2 City of Hope National Medical Center, Duarte, California, United States of America, 3 University of Maryland, Baltimore, Maryland, United States of America, 4 Saint Luke’s Mid America Heart Institute and the University of Missouri-Kansas City, Kansas City, Missouri, United States of America, 5 Burnham Institute for Medical Research, Orlando, Florida, United States of America, 6 University of North Carolina Institute for Pharmacogenomics and Individualized Therapy, Chapel Hill, North Carolina, United States of America Abstract Activation of peroxisome proliferator-activated receptor alpha (PPARa) occurs in animal models of diabetes (DM) and is implicated in pathological responses to myocardial ischemia. Using bioinformatics, we identified a single nucleotide polymorphism (SNP) in the PPARa gene promoter (PPARA 254,642 G.A; rs135561) that altered the consensus sequence for a nuclear receptor binding site. Electrophoretic mobility shift assays showed that the domain bound two known PPARA transcriptional activators, estrogen-related receptor (ERR)-a and -c and that PPARA G bound with greater affinity than PPARA A (.2-fold; P,0.05). Likewise, promoter-reporter analyses showed enhanced transcriptio