Impact of serotonin receptor 2A gene haplotypes on C-peptide levels in clozapine- and olanzapine-treated patients

• Objective Antagonism at the serotonin receptor 2A by the atypical antipsychotics clozapine and olanzapine has been suggested to be linked to these drugs' adverse effects on glucose-insulin homeostasis. Therefore, the aim of this study was to evaluate the impact of haplotypes based on the main functionally characterized polymorphisms of the serotonin receptor 2A (HTR2A) gene on parameters related to the glucose metabolism in clozapine-and olanzapine-treated patients. Methods Forty-nine patients, with schizophrenia or schizoaffective disorder and treated with clozapine (n = 22) or olanzapine (n = 27), were evaluated for fasting levels of C-peptide, insulin and blood glucose, homeostasis model assessment index for insulin resistance (HOMA-IR) and body mass index (BMI), and genotyped for the -1438A/G, -783A/G, 102T/C, and His452Tyr polymorphisms of the HTR2A gene. Results About 50% of the patients had elevated levels of C-peptide (>0.68 nmol/L) and insulin (>= 79 pmol/L). However, patients carrying the haplotype [-1438A, -783A, 102T, 452Tyr] had significantly lower C-peptide levels compared with patients not carrying this haplotype (p = 0.039), despite no differences in blood glucose, HOMA-IR or BMI between the patient groups. Conclusion Our results indicate that patients with the HTR2A haplotype [-1438A, -783A, 102T, 452Tyr] are less likely to develop metabolic abnormalities like C-peptide and insulin elevations during clozapine and olanzapine treatment. Copyright (C) 2010 John Wiley & Sons, Ltd.

Nyckelord

C-peptide

metabolic side effect

clozapine

olanzapine

serotonin receptor

single nucleotide polymorphism

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