A PPARα Promoter Variant Impairs ERR-Dependent Transactivation and Decreases Mortality after Acute Coronary Ischemia in Patients with Diabetes

Autor: Philip G. Jones, Daniel P. Kelly, Howard L. McLeod, Amber L. Beitelshees, Sharon Cresci, Gerald W. Dorn, Janice M. Huss, John A. Spertus, Matt R Minton
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Male
Diabetic Cardiomyopathies
Cardiovascular Disorders/Coronary Artery Disease
Myocardial Ischemia
Peroxisome proliferator-activated receptor
lcsh:Medicine
Coronary Disease
030204 cardiovascular system & hematology
Cohort Studies
Transactivation
0302 clinical medicine
Diabetic cardiomyopathy
Prospective Studies
Receptor
lcsh:Science
Promoter Regions
Genetic

chemistry.chemical_classification
0303 health sciences
Multidisciplinary
Genetics and Genomics/Functional Genomics
Middle Aged
3. Good health
Receptors
Estrogen

Female
Cardiovascular Disorders/Myocardial Infarction
Research Article
Protein Binding
Transcriptional Activation
medicine.medical_specialty
Genotype
Molecular Sequence Data
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide

03 medical and health sciences
Diabetes mellitus
Internal medicine
medicine
Humans
PPAR alpha
Diabetes and Endocrinology/Type 2 Diabetes
Allele frequency
030304 developmental biology
Aged
Base Sequence
lcsh:R
Genetic Variation
Promoter
medicine.disease
Endocrinology
chemistry
lcsh:Q
Molecular Biology/Translation Mechanisms
Zdroj: PLoS ONE
PLoS ONE, Vol 5, Iss 9, p e12584 (2010)
ISSN: 1932-6203
Popis: Activation of peroxisome proliferator-activated receptor alpha (PPARα) 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 PPARα gene promoter (PPARA -54,642 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)-α and -γ and that PPARA G bound with greater affinity than PPARA A (>2-fold; P
Databáze: OpenAIRE