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Article

Association of a Single-Nucleotide Variant rs11100494 of the NPY5R Gene with Antipsychotic-Induced Metabolic Disorders

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Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
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Shared Core Facilities “Molecular and Cell Technologies”, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia
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Department of Psychiatry and Addiction, Bashkir State Medical University, 450008 Ufa, Russia
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P.P. Kashchenko Saint Petersburg Psychiatric Hospital No. 1, Gatchinsky District, 190005 Leningrad, Russia
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Department of Psychotherapy and Sexology, I.I. Mechnikov North-Western State University, 191015 Saint Petersburg, Russia
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Saint Petersburg Postgraduate Institute of Medical Experts, 194044 Saint Petersburg, Russia
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Department of Psychiatry and Addiction, I.M. Pavlov First Saint Petersburg State Medical University, 197022 Saint Petersburg, Russia
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Department of General Medical Practice and Polyclinic Therapy, Siberian State Medical University, 634050 Tomsk, Russia
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International Centre for Education and Research in Neuropsychiatry, Samara State Medical University, 443099 Samara, Russia
*
Authors to whom correspondence should be addressed.
Academic Editors: Francisco Abad Santos and Pablo Zubiaur
Pharmaceutics 2022, 14(2), 222; https://doi.org/10.3390/pharmaceutics14020222
Received: 5 December 2021 / Revised: 12 January 2022 / Accepted: 13 January 2022 / Published: 18 January 2022
(This article belongs to the Special Issue Association Studies in Clinical Pharmacogenetics)
Background: The usage of antipsychotics (APs) is the most robust and scientifically based approach in the treatment of schizophrenia spectrum disorders (SSDs). The efficiency of APs is based on a range of target receptors of the central nervous system (CNS): serotoninergic, dopaminergic, adrenergic, histaminergic and cholinergic. Metabolic disorders are the most severe adverse drug reactions (ADRs) and lead to cardiovascular diseases with a high rate of mortality in patients with SSDs. Neuropeptide Y receptor Y5 (NPY5R) is known in the chain of interaction to target receptors for APs, agouti-related peptide receptors and proopiomelanocortin receptors. We studied the association of the single-nucleotide variants (SNVs) rs11100494 and rs6837793 of the NPY5R gene, and rs16147, rs5573, rs5574 of the NPY gene, with metabolic disorders in Russian patients with SSDs. Methods: We examined 99 patients with SSDs (mean age—24.56 years old). The mean duration of APs monotherapy was 8 weeks. The biochemical blood test included levels of glucose, cholesterol, lipoproteins, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein and albumin. Anthropometry included weight, height, waist circumference and hip circumference. We used real-time PCR to study the carriage of major and minor alleles of the SNV rs11100494 (1164C>A) of the NPY5R gene (chromosome localization—4q32.2). Group 1 comprised 25 patients with SSDs taking APs with a change in body weight of more than 6% since the start of APs therapy. Group 2 comprised 74 patients with SSDs taking APs with a change in body weight of less than 6% since the start of APs therapy. Results: We show the significance of genetic risk factors (carriage of major allele C of SNV rs11100494 of the NPY5R gene) for the development of AP-induced weight gain in Russian patients with SSDs. The allele C predisposes to AP-induced weight gain (OR = 33.48 [95% CI: 12.62; 88.82], p-value < 0.001). Additionally, the results of our study demonstrate that first-generation APs (FGAs) are more likely to cause an increase in serum transaminase levels but are less likely to increase body weight. Second-generation APs (SGAs) are more likely to cause weight gain and changes in serum glucose levels. Conclusion: Our study shows the predictive role of the allele C of SNV rs11100494 of the NPY5R gene in the development of AP-induced weight gain. However, we did not find a significant association between biochemical markers and this SNV in Russian patients with SSDs. View Full-Text
Keywords: pharmacogenetics; schizophrenia; NPYR; neuropeptide Y receptor; antipsychotic-induced weight gain; adverse drug reactions pharmacogenetics; schizophrenia; NPYR; neuropeptide Y receptor; antipsychotic-induced weight gain; adverse drug reactions
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MDPI and ACS Style

Dobrodeeva, V.S.; Shnayder, N.A.; Novitsky, M.A.; Asadullin, A.R.; Vaiman, E.E.; Petrova, M.M.; Limankin, O.V.; Neznanov, N.G.; Garganeeva, N.P.; Nasyrova, R.F. Association of a Single-Nucleotide Variant rs11100494 of the NPY5R Gene with Antipsychotic-Induced Metabolic Disorders. Pharmaceutics 2022, 14, 222. https://doi.org/10.3390/pharmaceutics14020222

AMA Style

Dobrodeeva VS, Shnayder NA, Novitsky MA, Asadullin AR, Vaiman EE, Petrova MM, Limankin OV, Neznanov NG, Garganeeva NP, Nasyrova RF. Association of a Single-Nucleotide Variant rs11100494 of the NPY5R Gene with Antipsychotic-Induced Metabolic Disorders. Pharmaceutics. 2022; 14(2):222. https://doi.org/10.3390/pharmaceutics14020222

Chicago/Turabian Style

Dobrodeeva, Vera S., Natalia A. Shnayder, Maxim A. Novitsky, Azat R. Asadullin, Elena E. Vaiman, Marina M. Petrova, Oleg V. Limankin, Nikolay G. Neznanov, Natalia P. Garganeeva, and Regina F. Nasyrova. 2022. "Association of a Single-Nucleotide Variant rs11100494 of the NPY5R Gene with Antipsychotic-Induced Metabolic Disorders" Pharmaceutics 14, no. 2: 222. https://doi.org/10.3390/pharmaceutics14020222

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