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The locus of the transcription factor 7\u2010like 2 (<jats:italic><jats:styled-content style=\"fixed-case\">TCF<\/jats:styled-content>7L2<\/jats:italic>) gene is strongly associated with type 2 diabetes (T2D). The goal of this study was to determine whether polymorphic <jats:italic><jats:styled-content style=\"fixed-case\">TCF<\/jats:styled-content>7L2<\/jats:italic> is involved in the susceptibility to the metabolic changes associated with the atypical antipsychotic agents (<jats:styled-content style=\"fixed-case\">AAP<\/jats:styled-content>s). In this study, a parallel clinical study with 3\u2010day consecutive administration of olanzapine (10 mg\/day) was conducted in 17 healthy subjects with a genotype of <jats:italic><jats:styled-content style=\"fixed-case\">TCF<\/jats:styled-content>7L2<\/jats:italic> rs7903146 <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> (N = 10) or <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> (N = 7). Olanzapine caused rapid metabolic changes including body\u2010weight gain, increased triglycerides level and reduced <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010cholesterol level in the healthy subjects. rs7093146 T carriers (<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>) were found to have greater <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>0\u20132 hr<\/jats:sub> of insulin during <jats:styled-content style=\"fixed-case\">OGTT<\/jats:styled-content> compared to those (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>) bearing only reference alleles before and after olanzapine treatment. However, the triglyceride level in the subjects with the <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> genotype was found to be significantly lower than that in the subjects with <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> 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 <jats:italic><jats:styled-content style=\"fixed-case\">TCF<\/jats:styled-content>7L2<\/jats:italic> polymorphism is a genetic risk factor of olanzapine\u2010associated metabolic side effects.<\/jats:p>","DOI":"10.1111\/bcpt.12727","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T15:59:39Z","timestamp":1481990379000},"page":"601-609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolic Response to Olanzapine in Healthy Chinese Subjects with rs7093146 Polymorphism in Transcription Factor 7\u2010like 2 Gene (<i><scp>TCF<\/scp>7L2<\/i>): A Prospective Study"],"prefix":"10.1111","volume":"120","author":[{"given":"Qing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Xiangya Hospital Central South University Hunan 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