[Brain neurotransmitter systems gene Polymorphism: the Search for pharmacogenetic markers of efficacy of haloperidol in Russians and Tatars]

Mol Biol (Mosk). 2015 Nov-Dec;49(6):959-67. doi: 10.7868/S0026898415050079.
[Article in Russian]

Abstract

Antipsychotics are the main drugs for the treatment of severe mental illness--schizophrenia affects about 1% of the population. The mechanism of action of neuroleptics is still up to the end. Several studies in the field of pharmacogenetics confirm enourmous influence of several neurotransmitter systems in the brain on the efficiency and the development of side effects. In this paper, we analyzed the association of nine polymorphic variants of five genes of dopaminergic and serotonergic systems DRD4, HTR2A, TPH1, SLC18A1, COMT in Russian and Tatars patients living in the Republic of Bashkortostan (RB) with the efficiency of a typical antipsychotic haloperidol on the scale of positive and negative systems of PANSS. The study established pharmacogenetic markers of increased and decreased effectiveness of therapy with haloperidol in the treatment groups. The results of this study confirm the importance of changes in the nucleotide sequences of the studied genes of the serotoninergic and dopaminergic systems (HTR2A, TPH1, SLC18A1 COMT, DRD4) in the formation of individual sensitivity to haloperidol. The results of our work considered as preliminary contact, requires an increase in the number of samples studied.

Keywords: antipsychotics; catechol-O-methyltransferase (COMT) gene; dopamine receptor (DRD4) gene; member 1 (SLC18A1); pharmacogenetics; schizophrenia; serotonin receptor (HTR2A) gene; solute transporter 18 family genes; tryptophan hydroxylase 1 (TPH1) gene.

Publication types

  • English Abstract

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Brain / drug effects
  • Brain / metabolism
  • Case-Control Studies
  • Catechol O-Methyltransferase / genetics
  • Female
  • Haloperidol / pharmacology*
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptor, Serotonin, 5-HT2A / genetics
  • Receptors, Dopamine D4 / genetics
  • Schizophrenia / drug therapy
  • Schizophrenia / ethnology
  • Schizophrenia / genetics*
  • Synaptic Transmission / genetics*
  • Tatarstan
  • Tryptophan Hydroxylase / genetics
  • Vesicular Monoamine Transport Proteins

Substances

  • Antipsychotic Agents
  • DRD4 protein, human
  • Receptor, Serotonin, 5-HT2A
  • SLC18A1 protein, human
  • Vesicular Monoamine Transport Proteins
  • Receptors, Dopamine D4
  • TPH1 protein, human
  • Tryptophan Hydroxylase
  • COMT protein, human
  • Catechol O-Methyltransferase
  • Haloperidol