Li Jiang, Hashimoto Hitoshi, Meltzer Herbert Y
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Evanston, IL, United States.
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Front Psychiatry. 2019 Feb 15;10:58. doi: 10.3389/fpsyt.2019.00058. eCollection 2019.
There is conflicting evidence for the association between genetic polymorphisms in the serotonin (5-HT) receptor (HTR2C) and response to antipsychotic drugs (APD) in schizophrenic patients. We tested the association between the HTR2C polymorphisms, Cys23Ser, -759C/T, and -697G/C, and response to APDs (mainly clozapine) in a 6 month prospective study in 171 patients with schizophrenia. Ser23 was significantly associated with treatment response (positive symptoms, = 7.540, = 0.01; negative symptoms, = 4.796, = 0.03) in male patients only. A -759C-Ser23 haplotype was similar associated with positive ( = 6.648, = 0.01) and negative ( = 6.702, = 0.01) symptom improvement. Logistic regression, after controlling for covariates, also showed significant haplotypic associations. A meta-analysis of six studies for Ser23 and treatment response showed an overall odds ratio of 2.00 (95%CI, 1.38-2.91, = 0.0003) or 1.94 (95%CI, 1.27-2.99, = 0.0024) under fixed or random effect models. These results provide additional evidence that HTR2C polymorphisms are associated with treatment response to APD with HTR2C antagonism or inverse agonism, in male schizophrenic patients.
关于精神分裂症患者中血清素（5 - HT）受体（HTR2C）基因多态性与抗精神病药物（APD）反应之间的关联，证据存在冲突。我们在一项针对171例精神分裂症患者的为期6个月的前瞻性研究中，测试了HTR2C基因多态性Cys23Ser、 - 759C/T和 - 697G/C与APD（主要是氯氮平）反应之间的关联。仅在男性患者中，Ser23与治疗反应（阳性症状， = 7.540， = 0.01；阴性症状， = 4.796， = 0.03）显著相关。一种 - 759C - Ser23单倍型与阳性（ = 6.648， = 0.01）和阴性（ = 6.702， = 0.01）症状改善类似相关。在控制协变量后进行的逻辑回归也显示出显著的单倍型关联。对六项关于Ser23与治疗反应的研究进行的荟萃分析显示，在固定效应或随机效应模型下，总体优势比为2.00（95%CI，1.38 - 2.91， = 0.0003）或1.94（95%CI，1.27 - 2.99， = 0.0024）。这些结果提供了额外的证据，表明在男性精神分裂症患者中，HTR2C基因多态性与具有HTR2C拮抗或反向激动作用的APD治疗反应相关。
