Abstract
Background
Antipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane) are described.
Objective
The objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol.
Patients and methods
The study included 64 male patients (average age 41.38 ± 10.14 years, median age 40 years, lower quintile [LQ] 35 years, upper quintile [UQ] 49 years). Bio-Rad CFX Manager™ software and “SNP-Screen” sets of “Syntol” (Russia) were used to determine polymorphisms rs4680, rs1800497, rs1124493, rs2242592, rs2298826 and rs2863170. In every “SNP-Screen” set, two allele-specific hybridizations were used, which allowed to determine two alleles of studied polymorphism separately on two fluorescence channels.
Results
Results of this study detected a statistically significant difference in the adverse drug reaction intensity in patients receiving haloperidol with genotypes 9/10 and 10/10 of polymorphic marker SLC6A3 rs28363170. In patients receiving haloperidol in tablets, the increases in the UKU Side-Effect Rating Scale (UKU) score of 9.96 ± 2.24 (10/10) versus 13 ± 2.37 (9/10; p < 0.001) and in the Simpson-Angus Scale (SAS) score of 5.04 ± 1.59 (10/10) versus 6.41 ± 1.33 (9/10; p = 0.006) were revealed.
Conclusion
Polymorphism of the SCL6A3 gene can affect the safety of haloperidol, and this should be taken into account during the choice of drug and its dosage regimen.
Acknowledgments
The authors are grateful to KB Mirzaev, JhA Avdeeva, JhA Sozaeva and NE Snalina at the research center of Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation for assistance in the genotyping of patients. This work was supported by the Russian Science Foundation (project 16-15-00227: “Fundamental research and exploratory research in priority areas of research”).
Disclosure
The authors report no conflicts of interest in this work.