Zastrozhin Mikhail Sergeevich, Brodyansky Vadim Markovich, Skryabin Valentin Yurievich, Grishina Elena Anatolievna, Ivashchenko Dmitry Vladimirovich, Ryzhikova Kristina Anatolievna, Savchenko Ludmila Mikhaylovna, Kibitov Alexander Olegovich, Bryun Evgeny Alekseevich, Sychev Dmitry Alekseevich
Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia.
Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Center for the Prevention of Dependent Behavior, Moscow, Russia.
Pharmgenomics Pers Med. 2017 Jul 7;10:209-215. doi: 10.2147/PGPM.S140700. eCollection 2017.
Antipsychotic action of haloperidol is due to blockade of D receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D 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 D receptors on the neuronal membrane) are described.
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.
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 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; < 0.001) and in the Simpson-Angus Scale (SAS) score of 5.04 ± 1.59 (10/10) versus 6.41 ± 1.33 (9/10; = 0.006) were revealed.
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.
氟哌啶醇的抗精神病作用是由于阻断中脑边缘多巴胺通路中的D受体，而药物不良反应则与纹状体D受体阻断有关。本文描述了关于编码这些受体及相关结构（儿茶酚-O-甲基转移酶[COMT]、甘氨酸转运体以及神经元膜上D受体密度的编码基因）的基因多态性影响的矛盾数据。
本研究的目的是评估DRD2、SLC6A3（DAT）和COMT基因多态性之间的相关性，并研究它们对接受氟哌啶醇治疗的酒精使用障碍患者药物不良反应发生情况的影响。
该研究纳入了64名男性患者（平均年龄41.38±10.14岁，中位数年龄40岁，下五分位数[LQ]35岁，上五分位数[UQ]49岁）。使用Bio-Rad CFX Manager™软件和俄罗斯“Syntol”公司的“SNP-Screen”试剂盒来确定rs4680、rs1800497、rs1124493、rs2242592、rs2298826和rs2863170基因多态性。在每个“SNP-Screen”试剂盒中，采用两种等位基因特异性杂交，可在两个荧光通道上分别确定所研究多态性的两个等位基因。
本研究结果检测到，接受氟哌啶醇治疗的具有多态性标记SLC6A3 rs28363170的9/10和10/10基因型患者的药物不良反应强度存在统计学显著差异。在接受氟哌啶醇片剂治疗的患者中，UKU副作用评定量表（UKU）评分升高，9.96±2.24（10/10）对比13±2.37（9/10；P<0.001），辛普森-安格斯量表（SAS）评分升高，5.04±1.59（10/10）对比6.41±1.33（9/10；P=0.006）。
SCL6A3基因多态性可能影响氟哌啶醇的安全性，在选择药物及其给药方案时应予以考虑。
