Genome-wide miRNA expression profiling of human lymphoblastoid cell lines identifies tentative SSRI antidepressant response biomarkers

Pharmacogenomics. 2012 Jul;13(10):1129-39. doi: 10.2217/pgs.12.93.

Abstract

Aim: Over 30% of patients with major depression do not respond well to first-line treatment with selective serotonin reuptake inhibitors (SSRIs). Using genome-wide expression profiling of human lymphoblastoid cell lines (LCLs) CHL1 was identified as a tentative SSRI sensitivity biomarker. This study reports on miRNAs implicated in SSRI sensitivity of LCLs.

Methods: Eighty LCLs were screened from healthy adult female individuals for growth inhibition by paroxetine. Eight LCLs exhibiting high or low sensitivities to paroxetine were chosen for genome-wide expression profiling with miRNA microarrays.

Results: The miRNA miR-151-3p had 6.7-fold higher basal expression in paroxetine-sensitive LCLs. This corresponds with lower expression of CHL1, a target of miR-151-3p. The additional miRNAs miR-212, miR-132, miR-30b*, let-7b and let-7c also differed by >1.5-fold (p < 0.05) between the two LCL groups.

Conclusion: The potential value of these miRNAs as tentative SSRI response biomarkers awaits validation with lymphocyte samples of major depression patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Pharmacological
  • Cell Adhesion Molecules* / genetics
  • Cell Adhesion Molecules* / metabolism
  • Cell Line, Transformed
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome, Human
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Paroxetine / pharmacology*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*

Substances

  • Biomarkers, Pharmacological
  • CHL1 protein, human
  • Cell Adhesion Molecules
  • MIRN151a microRNA, human
  • MicroRNAs
  • Serotonin Uptake Inhibitors
  • Paroxetine