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Characterization of statin dose response in electronic medical records.

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 a 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 preselected variants. Two large biobanks were used to construct dose-response curves for 2,026 and 2,252 subjects on simvastatin and atorvastatin, respectively. Atorvastatin was more efficacious, was more potent, and demonstrated less interindividual 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 subjects homozygous for the minor allele vs. 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 the genetic factors contributing to drug response.

SUBMITTER: Wei WQ

PROVIDER: S-EPMC3944214 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Characterization of statin dose response in electronic medical records.

Wei W-Q WQ Feng Q Q Jiang L L Waitara M S MS Iwuchukwu O F OF Roden D M DM Jiang M M Xu H H Krauss R M RM Rotter J I JI Nickerson D A DA Davis R L RL Berg R L RL Peissig P L PL McCarty C A CA Wilke R A RA Denny J C JC

Clinical pharmacology and therapeutics 20131004 3

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 a 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 preselected variants. Two large biobanks were used to construct dose-response curves for 2,026 and 2,252 subjects on simvastatin and atorvastati ...[more]

PMID: 24096969

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Characterization of statin dose response in electronic medical records.

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Characterization of statin dose response in electronic medical records.

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