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.
Wilke
Russell A
RA
Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA. rwilke@mcw.edu
Berg
Richard L
RL
Linneman
James G
JG
Zhao
Chengfeng
C
McCarty
Catherine A
CA
Krauss
Ronald M
RM
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