Kurylev Alexey A, Brodyansky Vadim M, Andreev Boris V, Kibitov Alexander O, Limankin Oleg V, Mosolov Sergey N
Department of clinical pharmacology, P.P. Kaschenko 1st City Mental Hospital. Leningrad region, Gatchinsky district, s. Nikolskoe, ul. Menkovskaya, 10., 188357, Saint-Petersburg, Russia,
Psychiatr Danub. 2018 Jun;30(2):157-163. doi: 10.24869/psyd.2018.157.
To assess the correlation between the antipsychotics (AP) mean daily doses, hospital stay duration and CYP2D6, DRD2 polymorphisms in naturalistic study.
CYP2D6 polymorphisms *3, *4, *5, *6, *1XN and DRD2/ANKK1 Taq1A polymorphisms were genotyped in a cohort of 226 Caucasian schizophrenic inpatients. AP daily doses, hospital stay duration and AP treatment duration were taken from medical records. To compare mean daily doses of AP among CYP2D6 PMs, EMs, UMs and DRD2/ANKK1 Taq1A carriers the actual AP doses were converted to chlorpromazine (CPZ) equivalents and DDD (defined daily dose).
Significant correlation (p=0.004) between CYP2D6 metabolic activity and AP mean daily doses was observed only among DRD2/ANKK1 Taq1A polymorphic allele carriers: 250.53 (95%CI: 154.90-346.17), 473.82 (95%CI: 426.99-520.64) 602.77 (95%CI: 469.65-735.88) CPZ equivalents in PMs, EMs and UMs, consequently. PMs with DRD2/ANKK1 Taq1A CT genotype received significantly lower doses of AP comparing to CC genotype (p=0.02). Mean hospital stay duration of PMs+UMs was significantly higher comparing to EMs (66.4 days (95% CI: 56.9-75.8) vs 50.2 days (95%CI: 45.5-54.7); p=0.047).
In a cohort of schizophrenia inpatients CYP2D6 metabolic activity affects mean AP daily dose only in the presence of DRD2 Taq1A polymorphic allele. CYP2D6 metabolic activity correlates independently from DRD2 Taq1A polymorphism with hospital stay duration. Subpopulation of schizophrenia inpatients with altered CYP2D6 activity (PMs and UMs) carriers of Taq1A polymorphisms needs special attention of clinicians in aligning of AP treatment.
在自然主义研究中评估抗精神病药物（AP）平均日剂量、住院时间与CYP2D6、DRD2基因多态性之间的相关性。
对226名白种人精神分裂症住院患者进行CYP2D6基因多态性*3、*4、*5、*6、*1XN以及DRD2/ANKK1 Taq1A基因多态性的基因分型。AP日剂量、住院时间和AP治疗时间均取自病历。为比较CYP2D6慢代谢型（PMs）、中代谢型（EMs）、快代谢型（UMs）以及DRD2/ANKK1 Taq1A携带者之间AP的平均日剂量，将实际AP剂量换算为氯丙嗪（CPZ）等效剂量和限定日剂量（DDD）。
仅在DRD2/ANKK1 Taq1A基因多态性等位基因携带者中观察到CYP2D6代谢活性与AP平均日剂量之间存在显著相关性（p = 0.004）：慢代谢型、中代谢型和快代谢型的CPZ等效剂量分别为250.53（95%CI：154.90 - 346.17）、473.82（95%CI：426.99 - 520.64）、602.77（95%CI：469.65 - 735.88）。携带DRD2/ANKK1 Taq1A CT基因型的慢代谢型患者与CC基因型相比，接受的AP剂量显著更低（p = 0.02）。慢代谢型和快代谢型患者的平均住院时间显著高于中代谢型患者（66.4天（95%CI：56.9 - 75.8） vs 50.2天（95%CI：45.5 - 54.7）；p = 0.047）。
在精神分裂症住院患者队列中，仅在存在DRD2 Taq1A基因多态性等位基因的情况下，CYP2D6代谢活性才会影响AP平均日剂量。CYP2D6代谢活性与住院时间独立相关，不受DRD2 Taq1A基因多态性影响。CYP2D6活性改变的精神分裂症住院患者亚群（慢代谢型和快代谢型），即Taq1A基因多态性携带者，在调整AP治疗时需要临床医生特别关注。
