Metabolic Response to Olanzapine in Healthy Chinese Subjects with rs7093146 Polymorphism in Transcription Factor 7-like 2 Gene (TCF7L2): A Prospective Study
Metabolic Response to Olanzapine in Healthy Chinese Subjects with rs7093146 Polymorphism in Transcription Factor 7-like 2 Gene (TCF7L2): A Prospective Study
复制标题
转录因子 7 样 2 基因 (TCF7L2) rs7093146 多态性的健康中国受试者对奥氮平的代谢反应：一项前瞻性研究
DOI：
10.1111/bcpt.12727
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发表时间：
2017-06-01
影响因子：
3.1
通讯作者：
Shu, Yan
中科院分区：
文献类型：
--
作者：
Li, Qing;Guo, Dong;Shu, Yan
奥氮平是一种广泛使用的非典型抗精神病药，体重显着增加和其他代谢副作用。转录因子7样2（TCF7L2）基因的基因座与2型糖尿病（T2D）密切相关。这项研究的目的是确定多态性TCF7L2是否参与与非典型抗精神病药（AAPS）相关的代谢变化的敏感性。在这项研究中，在17名健康受试者中进行了3天连续给予奥氮平（10 mg/day）的平行临床研究，该研究具有TCF7L2 RS7903146 CC（n = 10）或CT（n = 7）的健康受试者。奥氮平引起了快速的代谢变化，包括体重增加，甘油三酸酯水平升高和健康受试者的HDL-胆固醇水平降低。与仅在Olanzapine治疗前和之后仅具有参考等位基因的（CC）携带的（CC）相比，OGTT期间的rs7093146 t载体（CT）在OGTT期间具有更大的AUC（0-2小时）胰岛素。但是，发现患有CT基因型受试者中的甘油三酸酯水平明显低于CC基因型受试者的甘油三酸酯水平。此外，确定了基因型的作用与奥氮平对甘油三酸酯水平的影响之间的显着相互作用。急性奥氮平的治疗还显着导致健康受试者的总蛋白质，白蛋白和血红蛋白减少和尿酸增加。总之，即使急性奥氮平治疗也会引起显着和快速的代谢变化，而TCF7L2多态性也是奥氮平相关代谢副作用的遗传危险因素。
Olanzapine is a widely used atypical antipsychotic with significant weight gain and other metabolic side effects. The locus of the transcription factor 7-like 2 (TCF7L2) gene is strongly associated with type 2 diabetes (T2D). The goal of this study was to determine whether polymorphic TCF7L2 is involved in the susceptibility to the metabolic changes associated with the atypical antipsychotic agents (AAPs). In this study, a parallel clinical study with 3-day consecutive administration of olanzapine (10 mg/day) was conducted in 17 healthy subjects with a genotype of TCF7L2 rs7903146 CC (N = 10) or CT (N = 7). Olanzapine caused rapid metabolic changes including body-weight gain, increased triglycerides level and reduced HDL-cholesterol level in the healthy subjects. rs7093146 T carriers (CT) were found to have greater AUC(0-2 hr) of insulin during OGTT compared to those (CC) bearing only reference alleles before and after olanzapine treatment. However, the triglyceride level in the subjects with the CT genotype was found to be significantly lower than that in the subjects with CC genotype. Moreover, a significant interaction between the effect by genotype and that by olanzapine treatment on triglyceride level was identified. Acute olanzapine treatment also significantly caused total protein, albumin and haemoglobin decrease and uric acid increase in the healthy subjects. In conclusion, even acute olanzapine treatment induces significant and rapid metabolic changes, and TCF7L2 polymorphism is a genetic risk factor of olanzapine-associated metabolic side effects.