磺基转移酶4A1单倍型：关于其作为抗精神病药物反应生物标志物的作用存在相互矛盾的结果。

SULT4A1 haplotype: conflicting results on its role as a biomarker of antipsychotic response.

作者信息

Wang Dai, Li Qingqin, Favis Reyna, Jadwin Andrew, Chung Hedy, Fu Dong-Jing, Savitz Adam, Gopal Srihari, Cohen Nadine

机构信息

Neuroscience Therapeutic Area, Janssen Research & Development, LLC, 1125 Trenton Harbourton Rd, Titusville, NJ, USA.

出版信息

Pharmacogenomics. 2014;15(12):1557-64. doi: 10.2217/pgs.14.105.

DOI:10.2217/pgs.14.105

PMID:25340730

Abstract

AIM

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.

RESULTS

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.

CONCLUSION

Across three psychiatric disorders (n=2815 patients), we observed no consistent association between SULT4A1-1 status and atypical antipsychotic effect.

摘要

目的

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。

材料与方法

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。