Genetic Polymorphisms of Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia.

Background: Antipsychotic-induced metabolic syndrome (MetS) is a multifactorial disease with a genetic predisposition. Serotonin and its receptors are involved in antipsychotic-drug-induced metabolic disorders. The present study investigated the association of nine polymorphisms in the four 5-hydroxytryptamine receptor () genes , , , and and the gene encoding for the serotonin transporter with MetS in patients with schizophrenia.

Methods: A set of nine single-nucleotide polymorphisms of genes of the serotonergic system was investigated in a population of 475 patients from several Siberian regions (Russia) with a clinical diagnosis of schizophrenia. Genotyping was performed and the results were analyzed using chi-square tests.

Results: Polymorphic variant rs521018 () was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. Rs1150226 () was also associated but did not meet Hardy-Weinberg equilibrium.

Conclusions: Our results indicate that allelic variants of genes may have consequences on metabolic parameters. MetS may have too complex a mechanistic background to be studied without dissecting the syndrome into its individual (causal) components.