title: 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 AUC0-2 hrof 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.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, Baltimore, MD, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, Baltimore, MD, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, Baltimore, MD, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000097:blood / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D000077152:Olanzapine; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D014527:Uric Acid / Q000097:blood
chemical_list: D014150:Antipsychotic Agents; D007328:Insulin; D008055:Lipids; D058118:Transcription Factor 7-Like 2 Protein; D001569:Benzodiazepines; D014527:Uric Acid; D000077152:Olanzapine