Polymorphism of brain neurotransmitter system genes: Search for pharmacogenetic markers of haloperidol efficiency in Russians and Tatars

Antipsychotics are the primary drugs for treating schizophrenia, a severe psychical disease that affects approximately 1% of the population. The mechanism of antipsychotic action has not yet been completely clarified. A number of studies in the field of pharmacogenetics have confirmed the huge influence of several neurotransmitter systems on the efficiency and development of side effects. In the present work, we studied whether there are associations between nine polymorphic variants of five genes of dopaminergic and serotonergic systems (DRD4, HTR2A, TPH1, SLC18A1, and COMT) in schizophrenia patients (Russians and Tatars) and the efficiency of therapy by haloperidol (a typical antipsychotic) according to the positive and negative syndrome scale (PANSS). Interethnic differences in the specificity of genetic factors of sensitivity to haloperidol therapy have been registered. Pharmacogenetic markers of increased and decreased efficiency of the therapy by this drug were established in patients of Russian ethnicity. No genetic markers of the efficiency of haloperidol therapy in the studied genes have been detected in patients of Tatar ethnicity. These results confirm the significance of changes in nucleotide sequences of all studied dopaminergic and serotonergic system genes in the development of individual sensitivity to haloperidol. We consider our data to be preliminary (before their confirmation on larger patient samples).