lunes, 21 de octubre de 2013

Characterization of Statin Dose-response... [Clin Pharmacol Ther. 2013] - PubMed - NCBI

Characterization of Statin Dose-response... [Clin Pharmacol Ther. 2013] - PubMed - NCBI

Clin Pharmacol Ther. 2013 Oct 4. doi: 10.1038/clpt.2013.202. [Epub ahead of print]

Characterization of Statin Dose-response within Electronic Medical Records.

Source

Department of Biomedical Informatics, Vanderbilt University, Nashville, TN.

Abstract

Efforts to define the genetic architecture underlying variable statin response have met with limited success possibly because previous studies were limited to effect based on one-single-dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 pre-selected variants. Two large biobanks were used to construct dose-response curves for 2,026 (simvastatin) and 2,252 subjects (atorvastatin). Atorvastatin was more efficacious, more potent, and demonstrated less inter-individual variability than simvastatin. A pharmacodynamic variant emerging from randomized trials (PRDM16) was associated with Emax for both. For atorvastatin, Emax was 51.7 mg/dl in homozygous for the minor allele versus 75.0 mg/dl for those homozygous for the major allele. We also identified several loci associated with ED50. The extraction of rigorously defined traits from EMRs for pharmacogenetic studies represents a promising approach to further understand of genetic factors contributing to drug response.Clinical Pharmacology & Therapeutics (2013); Accepted article preview online 4 October 2013; doi:10.1038/clpt.2013.202.
PMID:
24096969
[PubMed - as supplied by publisher]

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