CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: results from the Munich Antidepressant Response Signature (MARS) study

Pharmacogenomics. 2015;16(7):689-701. doi: 10.2217/pgs.15.31. Epub 2015 May 6.

Abstract

Aim: The identification of antidepressant drugs (ADs) response biomarkers in depression is of high clinical importance. We explored CHL1 and ITGB3 expression as tentative response biomarkers.

Materials & methods: In vitro sensitivity to ADs, as well as gene expression and genetic variants of the candidate genes CHL1, ITGB3 and SLC6A4 were measured in lymphoblastoid cell lines (LCLs) of 58 depressed patients.

Results: An association between the clinical remission of depression and the basal expression of CHL1 and ITGB3 was discovered. Individuals whose LCLs expressed higher levels of CHL1 or ITGB3 showed a significantly better remission upon AD treatment. In addition individuals with the CHL1 rs1516338 TT genotype showed a significantly better remission after 5 weeks AD treatment than those carrying a CC genotype. No association between the in vitro sensitivity of LCLs toward AD and the clinical remission could be detected.

Conclusion: CHL1 expression in patient-derived LCLs correlated with the clinical outcome. Thus, it could be a valid biomarker to predict the success of an antidepressant therapy. Original submitted 8 December 2014; Revision submitted 2 March 2015.

Keywords: CHL1; ITGB3; MARS; Munich Antidepressant Response Signature Project; depression; gene expression; imipramine; lymphoblastoid cell line; mirtazapine; paroxetine; response biomarker.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Biomarkers, Pharmacological / metabolism
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / epidemiology
  • Depressive Disorder, Major / genetics*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation
  • Germany / epidemiology
  • Humans
  • Integrin beta3 / biosynthesis
  • Integrin beta3 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Serotonin Plasma Membrane Transport Proteins / biosynthesis
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Switzerland / epidemiology
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Biomarkers, Pharmacological
  • CHL1 protein, human
  • Cell Adhesion Molecules
  • ITGB3 protein, human
  • Integrin beta3
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins