title: The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia.
abstract: The use of antipsychotics is associated with metabolic side effects, which put patients with schizophrenia or related disorders at risk for cardiovascular morbidity. The high interindividual variability in antipsychotic-induced metabolic abnormalities suggests that genetic makeup is a possible determinant. In this cross-sectional study, we investigated whether genotypes of the HTR2C receptor are associated with the metabolic syndrome in patients using antipsychotics. Patients were identified from a schizophrenia disease management program. In this program, patients' blood pressure, triglycerides, high-density lipoprotein-cholesterol, and waist circumference are measured regularly during follow-up. The primary end point of our study was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the HTR2C receptor gene (HTR2C:c.1-142948[GT]n, rs3813928 [-997 G/A], rs3813929 [-759 C/T], rs518147 [-697 G/C], and rs1414334 [C > G]). The included patients (n = 112) mainly (>80%) used atypical antipsychotics (clozapine, olanzapine, and risperidone). Carriership of the variant alleles of the HTR2C polymorphisms rs518147, rs1414334, and HTR2C:c.1-142948(GT)n was associated with an increased risk of the metabolic syndrome (adjusted odds ratio [OR], 2.62 [95% confidence interval {CI}, 1.00-6.85]; OR, 4.09 [95% CI, 1.41-11.89]; and OR, 3.12 [95% CI, 1.13-8.16]), respectively. Our findings suggest that HTR2C genotypes are associated with antincreased risk of metabolic syndrome in patients taking antipsychotics.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Mulder
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Annemarie Aart
authors.initials: AA
authors.lastname: van der-Beek van der
authors.forename: Johan
authors.initials: J
authors.lastname: Arends
authors.forename: Frederik W
authors.initials: FW
authors.lastname: Wilmink
authors.forename: Hans
authors.initials: H
authors.lastname: Scheffer
authors.forename: Antoine C G
authors.initials: AC
authors.lastname: Egberts
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D004247:DNA