Metabolic Response to Olanzapine in Healthy Chinese Subjects with rs7093146 Polymorphism in Transcription Factor 7‐like 2 Gene ( TCF 7L2): A Prospective Study

作者：Qing Li, Dong Guo, Hong Yang, Zhi Ye, Jin Huang, Yan Shu · 发表于：Basic & Clinical Pharmacology & Toxicology · 年份：2016 · DOI：10.1111/bcpt.12727 · 被引用次数：4 · 研究领域：Diabetes Treatment and Management、Pancreatic function and diabetes、Bipolar Disorder and Treatment

Abstract 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 ( TCF 7L2 ) gene is strongly associated with type 2 diabetes (T2D). The goal of this study was to determine whether polymorphic TCF 7L2 is involved in the susceptibility to the metabolic changes associated with the atypical antipsychotic agents ( AAP s). 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 TCF 7L2 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 ch...