VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls

Br J Psychiatry. 2016 Aug;209(2):114-20. doi: 10.1192/bjp.bp.115.161950. Epub 2016 Mar 3.

Abstract

Background: Common variants in the Vaccinia-related kinase 2 (VRK2) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear.

Aims: To identify potential differences in VRK2 gene expression levels between schizophrenia, bipolar disorder, psychosis not otherwise specified (PNOS) and healthy controls.

Method: VRK2 mRNA level was measured in whole blood in 652 individuals (schizophrenia, n = 201; bipolar disorder, n = 167; PNOS, n = 61; healthy controls, n = 223), and compared across diagnostic categories and subcategories. Additionally, we analysed for association between 1566 VRK2 single nucleotide polymorphisms and mRNA levels.

Results: We found lower VRK2 mRNA levels in schizophrenia compared with healthy controls (P<10(-12)), bipolar disorder (P<10(-12)) and PNOS (P = 0.0011), and lower levels in PNOS than in healthy controls (P = 0.0042) and bipolar disorder (P = 0.00026). Expression quantitative trait loci in close proximity to the transcription start site of the short isoforms of the VRK2 gene were identified.

Conclusions: Altered VRK2 gene expression seems specific for schizophrenia and PNOS, which is in accordance with findings from genome-wide association studies. These results suggest that reduced VRK2 mRNA levels are involved in the underlying mechanisms in schizophrenia spectrum disorders.

MeSH terms

  • Adult
  • Bipolar Disorder / genetics*
  • Female
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Protein Serine-Threonine Kinases / metabolism*
  • Psychotic Disorders / genetics*
  • RNA, Messenger
  • Schizophrenia / genetics*

Substances

  • RNA, Messenger
  • Protein Serine-Threonine Kinases
  • VRK2 protein, human