The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia.
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.
Mulder
Hans
H
Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Franke
Barbara
B
van der-Beek van der
Annemarie Aart
AA
Arends
Johan
J
Wilmink
Frederik W
FW
Scheffer
Hans
H
Egberts
Antoine C G
AC
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
D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D004247:DNA