DRD2、DRD3和HTR2A单核苷酸多态性与非典型抗精神病药物的高治疗抗性有关。
DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.
作者信息
Del Casale Antonio, Simmaco Maurizio, Modesti Martina Nicole, Zocchi Clarissa, Arena Jan Francesco, Bilotta Irene, Alcibiade Alessandro, Sarli Giuseppe, Cutillo Lorenzo, Antonelli Giulia, La Spina Enrico, De Luca Ottavia, Preissner Robert, Borro Marina, Gentile Giovanna, Girardi Paolo, Pompili Maurizio
机构信息
Department of Dynamic and Clinical Psychology and Health Studies, Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy.
Unit of Psychiatry, 'Sant'Andrea' University Hospital, 00189 Rome, Italy.
出版信息
Biomedicines. 2023 Jul 24;11(7):2088. doi: 10.3390/biomedicines11072088.
BACKGROUND
The objective of this study was to investigate the rs1800497, rs1799732, rs1801028, rs6280, and rs6314, rs7997012, and rs6311 single-nucleotide polymorphism (SNP) correlations with resistance to second-generation antipsychotics (SGAs) in a real-world sample of patients with treatment-resistant mental disorders.
METHODS
We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozapine, or classic neuroleptics for a failure of previous SGAs trials) and a low treatment resistance (LTR) group (current treatment with one atypical antipsychotic). We used Next-Generation Sequencing on DNA isolated from peripheral blood samples to analyze the polymorphisms. We performed logistic regression to search for predictors of HTR membership.
RESULTS
A diagnosis of schizophrenia significantly predicted the HTR membership compared to other diagnoses. Other predictors were the rs6280 C|T (OR = 22.195) and T|T (OR = 18.47) vs. C|C, rs7997012 A|G vs. A|A (OR = 6.859) and vs. G|G (OR = 2.879), and rs1799732 I|I vs. D|I (OR = 12.079) genotypes.
CONCLUSIONS
A diagnosis of schizophrenia and the rs1799732, rs6280, and rs7997012 genotypes can predict high treatment resistance to SGAs.
背景
本研究的目的是在治疗抵抗性精神障碍患者的真实样本中，调查rs1800497、rs1799732、rs1801028、rs6280、rs6314、rs7997012和rs6311单核苷酸多态性（SNP）与第二代抗精神病药物（SGA）耐药性的相关性。
方法
我们将129名参与者分为高治疗抵抗（HTR）组（目前使用两种SGA、氯氮平或经典抗精神病药物治疗，此前SGA试验失败）和低治疗抵抗（LTR）组（目前使用一种非典型抗精神病药物治疗）。我们对外周血样本中分离的DNA进行二代测序，以分析多态性。我们进行逻辑回归以寻找HTR组成员的预测因素。
结果
与其他诊断相比，精神分裂症诊断显著预测了HTR组成员身份。其他预测因素为rs6280 C|T（OR = 22.195）和T|T（OR = 18.47）与C|C相比、rs7997012 A|G与A|A相比（OR = 6.859）以及与G|G相比（OR = 2.879），以及rs1799732 I|I与D|I相比（OR = 12.079）基因型。
结论
精神分裂症诊断以及rs1799732、rs6280和rs7997012基因型可预测对SGA的高治疗抵抗性。
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