Characterization of low-density lipoprotein cholesterol-lowering efficacy for atorvastatin in a population-based DNA biorepository.
The Marshfield Clinic Personalized Medicine Research Project (PMRP) represents a large population-based biobank located in central Wisconsin. To position the PMRP database for large-scale pharmacogenetic association studies in the context of lipid-lowering therapy, we constructed an electronic phenotyping algorithm to quantify exposure and dose-response for atorvastatin, the most commonly prescribed lipid-lowering agent within this population. The resulting datasets were used to generate five distinct parameters for atorvastatin-induced changes in low-density lipoprotein (LDL) cholesterol level: (i) pretreatment, baseline LDL level [E(0)]; (ii) absolute reduction in LDL; (iii) relative reduction in LDL; (iv) potency [ED(50)]; and (v) maximal efficacy [E(max)]. These parameters will facilitate the efficient application of electronic phenotyping for drug outcomes in the context of large pharmacogenetic association studies.
Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA. rwilke@mcw.edu
Russell A
RA
Wilke
Richard L
RL
Berg
James G
JG
Linneman
Chengfeng
C
Zhao
Catherine A
CA
McCarty
Ronald M
RM
Krauss
D000465:Algorithms; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood* / Q000378:metabolism; D015331:Cohort Studies; D004247:DNA; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005828:Genetics, Population; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008499:Medical Records; D015999:Multivariate Analysis; D010597:Pharmacogenetics / Q000379:methods*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D004247:DNA; D000069059:Atorvastatin