Identifying genetic modulators of statin response using subject-derived lymphoblastoid cell lines

Pharmacogenomics. 2021 May;22(7):413-421. doi: 10.2217/pgs-2020-0197. Epub 2021 Apr 16.

Abstract

Although statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) have proven effective in reducing plasma low-density lipoprotein levels and risk of cardiovascular disease, their lipid lowering efficacy is highly variable among individuals. Furthermore, statin treatment carries a small but significant risk of adverse effects, most notably myopathy and new onset diabetes. Hence, identification of biomarkers for predicting patients who would most likely benefit from statin treatment without incurring increased risk of adverse effects can have a significant public health impact. In this review, we discuss the rationale for the use of subject-derived lymphoblastoid cell lines in studies of statin pharmacogenomics and describe a variety of approaches we have employed to identify novel genetic markers associated with interindividual variation in statin response.

Keywords: RNA-seq; SNP; cellular model; functional genetics; interindividual variation; lymphoblastoid cell lines; pharmacogenomics; statin; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Line
  • Gene Expression Profiling
  • Genetic Markers / genetics
  • Genotype
  • Haplotypes
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • Transcriptome
  • Treatment Outcome

Substances

  • Genetic Markers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors