Abstract
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 (HTR) genes HTR1A, HTR2A, HTR3A, and HTR2C and the gene encoding for the serotonin transporter SLC6A4 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 (HTR2C) was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. Rs1150226 (HTR3A) was also associated but did not meet Hardy–Weinberg equilibrium. Conclusions: Our results indicate that allelic variants of HTR2C 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.
Highlights
Antipsychotics are important therapeutic agents for patients with schizophrenia, but long-term use of these drugs increases the risk of developing type 2 diabetes mellitus, hyperlipidemia, and hypertension [1,2,3,4,5,6]
These drugs are known to increase the prevalence of metabolic syndrome (MetS), which is a clustering of well-known cardiovascular risk factors and is known to be augmented in a variety of psychiatric disorders [6]
Metabolic syndrome was diagnosed in 126 patients (26.5%)
Summary
Antipsychotics are important therapeutic agents for patients with schizophrenia, but long-term use of these drugs increases the risk of developing type 2 diabetes mellitus, hyperlipidemia, and hypertension [1,2,3,4,5,6] These drugs are known to increase the prevalence of metabolic syndrome (MetS), which is a clustering of well-known cardiovascular risk factors and is known to be augmented in a variety of psychiatric disorders [6]. The present study investigated the association of nine polymorphisms in the four 5-hydroxytryptamine receptor (HTR) genes HTR1A, HTR2A, HTR3A, and HTR2C and the gene encoding for the serotonin transporter SLC6A4 with MetS in patients with schizophrenia. Results: Polymorphic variant rs521018 (HTR2C) was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. MetS may have too complex a mechanistic background to be studied without dissecting the syndrome into its individual (causal) components
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