Genetic Polymorphisms in the HTR2C and Peroxisome Proliferator-Activated Receptors Are Not Associated with Metabolic Syndrome in Patients with Schizophrenia Taking Clozapine

Psychiatry Investig. 2011 Sep;8(3):262-8. doi: 10.4306/pi.2011.8.3.262. Epub 2011 May 26.

Abstract

Objective: Genetic variation in the serotonin-2C receptor encoded by the HTR2C gene is one of the genetic determinants of antipsychotic-induced weight gain. Peroxisome proliferator-activated receptors are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. In this cross-sectional study, we investigated whether HTR2C-759C/T, HTR2C-697G/C, PPARα V227A, and PPARγ 161C/T genotypes were associated with metabolic syndrome (MetS) in patients with schizophrenia taking clozapine.

Methods: One hundred forty-six Korean patients using clozapine for more than one year were genotyped for the HTR2C-759C/T, HTR2C-697G/C, PPARα V227A, and PPARγ 161C/T polymorphisms, and their weight, waist circumference, blood pressure, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, and glucose were measured. We used the criteria for MetS proposed by the National Cholesterol Education Program-adapted Adult Treatment Panel III.

Results: The prevalence of MetS was 47.3% and was similar among men (49%) and women (42.9%). We found no significant differences between patients with and without MetS in terms of genotypes or allele frequencies. Logistic regression analyses also revealed no association between MetS and each genotype.

Conclusion: We did not find significant associations between four polymorphisms (HTR2C-759C/T, HTR2C-697G/C, PPARα V227A, and PPARγ 161C/T) and MetS in patients with schizophrenia taking clozapine.

Keywords: Clozapine; HTR2C; Metabolic syndrome; PPAR; Polymorphism; Schizophrenia.