Wang Dai, Li Qingqin, Favis Reyna, Jadwin Andrew, Chung Hedy, Fu Dong-Jing, Savitz Adam, Gopal Srihari, Cohen Nadine
Neuroscience Therapeutic Area, Janssen Research & Development, LLC, 1125 Trenton Harbourton Rd, Titusville, NJ, USA.
Pharmacogenomics. 2014;15(12):1557-64. doi: 10.2217/pgs.14.105.
Based on previous pharmacogenetic findings, we investigated the possible association between SULT4A1-1 haplotype and antipsychotic treatment response.
MATERIALS & METHODS: Using Mixed Model Repeated Measures, we tested the relationship between SULT4A1-1 status (+carrier, -noncarrier) and clinical improvement (in Positive and Negative Syndrome Scale total score) among European ancestry patients treated with paliperidone extended release (n=937), paliperidone palmitate (n=990), risperidone (n=507) and olanzapine (n=381) in 12 schizophrenia, two schizoaffective disorder and three bipolar I disorder trials. SULT4A1-1 haplotype was determined using tagging SNP rs763120.
There was no significant difference between SULT4A1-1(+) and SULT4A1-1(-) patients for treatment response to paliperidone or olanzapine. SULT4A1-1(-) patients had better treatment response to risperidone in one schizophrenia trial, but not in another schizophrenia trial or bipolar mania trial.
Across three psychiatric disorders (n=2815 patients), we observed no consistent association between SULT4A1-1 status and atypical antipsychotic effect.
基于先前的药物遗传学研究结果，我们调查了SULT4A1-1单倍型与抗精神病药物治疗反应之间的可能关联。
在12项精神分裂症、2项分裂情感性障碍和3项双相I型障碍试验中，我们使用混合模型重复测量法，测试了接受帕利哌酮缓释片（n = 937）、棕榈酸帕利哌酮（n = 990）、利培酮（n = 507）和奥氮平（n = 381）治疗的欧洲血统患者中SULT4A1-1状态（+携带者，-非携带者）与临床改善（阳性和阴性症状量表总分）之间的关系。使用标签单核苷酸多态性rs763120确定SULT4A1-1单倍型。
SULT4A1-1（+）和SULT4A1-1（-）患者对帕利哌酮或奥氮平的治疗反应没有显著差异。在一项精神分裂症试验中，SULT4A1-1（-）患者对利培酮的治疗反应更好，但在另一项精神分裂症试验或双相躁狂试验中并非如此。
在三种精神疾病（n = 2815例患者）中，我们观察到SULT4A1-1状态与非典型抗精神病药物疗效之间没有一致的关联。
