Metabolic Response to Olanzapine in Healthy Chinese Subjects with rs7093146 Polymorphism in Transcription Factor 7‐like 2 Gene (TCF7L2): A Prospective Study

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 (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 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.

Olanzapine Promotes the Occurrence of Metabolic Disorders in Conditional TCF7L2-Knockout Mice

“…In the present study, we found that Tcf7l2 CKO mice present higher body weight growth rate when exposed to olanzapine. This is consistent with recent clinical observation that healthy Chinese people with TCF7L2 rs7093146 have larger increment of weight gain when treated with olanzapine (10 mg/d) ( Li et al, 2017 ). These results strongly indicate that TCF7L2 is highly likely to be involved in the body weight management regulated by olanzapine.…”

Prevalence and risk factors of hyperuricemia among patients with schizophrenia in a public psychiatric hospital in China

“…Several studies found that olanzapine was associated with elevated uric acid in patients with schizophrenia, patients with bipolar disorder and healthy subjects. [21][22][23][24] Though the data of antipsychotics use were not available in our study, most of the patients received antipsychotics treatment before they admitting this hospital. Moreover, risperidone and olanzapine were the most frequently used antipsychotics in Chinese patients with schizophrenia.…”