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. 2021 Mar 5;11(3):181.
doi: 10.3390/jpm11030181.

Genetic Polymorphisms of 5-HT Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia

Diana Z Paderina  1 , Anastasiia S Boiko  1 , Ivan V Pozhidaev  1 , Anna V Bocharova  2 , Irina A Mednova  1 , Olga Yu Fedorenko  1 , Elena G Kornetova  1   3 , Anton J M Loonen  4 , Arkadiy V Semke  1 , Nikolay A Bokhan  1   3 , Svetlana A Ivanova  1   3
Affiliations

Genetic Polymorphisms of 5-HT Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia

Diana Z Paderina et al. J Pers Med. .

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.

Keywords: antipsychotics; body mass index; genes; metabolic syndrome; pharmacogenetics; schizophrenia; serotonin; weight gain.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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