Association Between HTR2C and HTR2A Polymorphisms and Metabolic Abnormalities in Patients Treated With Olanzapine or Clozapine

Serotonin 2C and 2A receptor (5-HT2C and 5-HT2A) antagonisms are hypothesized to play a role in the metabolic adverse effects induced by olanzapine and clozapine, Associations between polymorphisms in 5-HT2C, and 5-HT2A receptor coding genes, HTR2C and HTR2A. with antipsychotic-induced weight gain have been reported. The impact of HTR2C and HTR2-1 polymorphisms oil body mass index (BMI). glucose-insulin homeostasis, and blood lipid levels was evaluated in 46 patients with schizophrenia or schizoaffective disorder and treated with olanzapine (n = 28) or clozapine (n = 18) for at least 6 months. Olanzapine-treated patients with HTR2C haplotype C (-759C. -697C. and 23Ser) had higher BMI (P = 0.029) an(] C peptide levels (P = 0.029) compared with patients with haplotype B -759T. -697C. and 23Cys). The frequency of patients homozygous for the HTR2C haplotype A (-759C. -697G. and 23Cys) was significantly higher among clozapine-treated patients with obesity (BMI >= 30 kg/m(2)) compared with nonobese patients (11 = 0.015 odds ratio, 28; 95% confidence interval. 2-380). Patients carrying the HTR2A haplotype 2(-1438A. 102T, and 452His) had significantly higher C peptide levels compared with haplotype 3 (-1438A, 102T, and 452Tyr) carriers in the olanzapine group (P = 0.034) and in the overall study population (P = 0.019). None of the haplotypes were associated with serum levels of insulin. triglycerides, and cholesterol or with homeostasis model assessment index for insulin resistance. In conclusion, both HTR2C and HTR. 4 gene polymorphisms seem to be associated with the occurrence of metabolic abnormalities in patients treated with olanzapine or clozapine.