Olanzapine-induced Metabolic Syndrome and its Association with -759C>T Polymorphism of the HTR2C Gene in Iraqi Schizophrenic Patients

Authors

DOI:

https://doi.org/10.31351/vol33iss3pp37-46

Abstract

The hazardous metabolic effects of treating schizophrenia patients with olanzapine comprise serotonin 2C receptor (5-HT2C) antagonists. Metabolic side effects of antipsychotic drugs, including lipid abnormalities, disturbed glucose metabolism, and weight gain, can have a major impact on treating psychiatric patients. The intent of this study was to investigate whether there is an associated link between the genetic polymorphism at -759C>T in the promoter region of the 5-hydroxytryptamine 2C receptor (HTR2C) gene and the metabolic syndrome driven by olanzapine in schizophrenia patients. A cross-sectional study that involved fifty hospitalized patients with schizophrenia. The patients were split into two groups (metabolic and non-metabolic) according to the classification criteria of the metabolic syndrome. The HTR2C promoter region polymorphism was identified through sequencing using the Sanger method after polymerase chain reaction amplification of the extracted deoxyribonucleic acid. Even though none of the genotypes of the -759C>T variant are associated with the propensity to develop metabolic syndrome, there is a significant difference in the -759C>T variant's T allele (p-value = 0.001). The presence of the T allele in the -759 C/T variant was significantly associated with developing metabolic syndrome.

Keywords: Schizophrenic patients, Olanzapine, Genetic polymorphism, 5-hydroxytryptamine 2C receptor (HTR2C) gene, -759C>T.

 

Author Biography

  • Samer Imad Mohammed, Department of Clinical Pharmacy, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

     

     

References

Younis MS, Mahdi A alrubayee F. Attitude of Medical Students University of Baghdad toward Psychiatry:Clinical significance and as future career. Journal of the Faculty of Medicine Baghdad. 2019 May 12;60(4):222–7.

Mahmood MK, Anwer ZM. The Prevalence of Potentially Inappropriate Prescribing in Geriatric Patients with Psychiatric Disorders in Iraq. Iraqi Journal of Pharmaceutical Sciences (P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512). 2020 Jun 25;29(1):166–73.

Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. Journal of the American Medical Association. 2002 Dec 4;288(21):2709–16.

G Jameel M, Alhakeem ZM, Al-Osami MH. Prevalence of AGER gene polymorphism in post menopause Iraqi sample with Osteoporosis and osteopenia in type 2DM. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512). 2022 Dec 24;31(2):202–10.

Hobart M. Medical Illness and Schizophrenia, 2nd editionedited by Jonathan M. Meyer, M.D., and Henry A. Nasrallah, M.D.; Arlington, Virginia, American Psychiatric Publishing, Inc., 2009, 471 pages. Psychiatric Services. 2010 May;61(5):533–533.

Elena Kornetova Alexander Kornetov Marina Arzhanik Svetlana A. Ivanova. Metabolic syndrome in patients with schizophrenia receiving atypical antipsychotics. 27th European Congress of Psychiatry. 2019

Chen Y, Wang Y, Fang X, Zhang Y, Song L, Zhang C. Association of the HTR2C-759C/T polymorphism and antipsychotic-induced weight gain: A meta-analysis. Gen Psychiatr. 2020 May 14;33(3).

Munim Al-Thanoon ZA, Mahmood IH. Metabolic changes caused by first generation antipsychotic versus second generation antipsychotic in schizophrenic patients. Journal of Pharmacy Research. 2013 Jun;7(6):468–71.

Dizaye K, Hassan M, Ali S. Effects of Olanazapine and Haloperidol on Serum Malondialdehyde, Prolactin Level, Blood Glucose and Lipid Profile in Schizophrenic Patients. Zanco Journal of Medical Sciences. 2010 Aug 1;14(2):13–21.

Zinah Abdulhameed Alobaidi, & Samer Imad Mohammed. (2023). The Association Between -697C>G and -997G>A polymorphism of the HTR2C Gene and the Metabolic Syndrome in Iraqi Schizophrenic Patients. Journal of Population Therapeutics and Clinical Pharmacology, 30(9), 271–282.

Al-Hemiary NJ, Hashim MT, Al-Shawi AF, Al-Diwan JK. Effect of post-traumatic stress disorder on school achievement among secondary school students in Baghdad, Iraq. Journal of the Faculty of Medicine Baghdad. 2016 Jul 3;58(2):146–8.

Gaebel W, Zielasek J. Schizophrenia in 2020: Trends in diagnosis and therapy. Psychiatry and Clinical Neurosciences. 2015 Jul 1;69(11):661–73.

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome. Current Opinion in Cardiology. 2006 Jan;21(1):1–6.

Mahmood A, Ahmed M, Mohammad J. Prevalence of metabolic syndrome in angiographically confirmed coronary artery disease. Medical Journal of Babylon. 2018;15(4):310.

Alobaidi ZA, Mohammed SI. Association of Disease Duration and Duration of Olanzapine Use with Blood Sugar, Blood Pressure, BMI, and Lipid Profile among Schizophrenic Patients in Iraq. Al-Rafidain Journal of Medical Sciences (ISSN 2789-3219). 2023 Jun 5;4:79-85.

Daray FM, Rodante D, Carosella LG, Silva ME, Martínez M, Busch MVF, et al. -759C > T polymorphism of the HTR2C gene is associated with second-generation antipsychotic-induced weight gain in female patients with schizophrenia. Pharmacopsychiatry. 2017 Jan 1;50(1):14–8.

Cohn T, Prud’homme D, Streiner D, Kameh H, Remington G. Characterizing coronary heart disease risk in chronic schizophrenia: High prevalence of the metabolic syndrome. Canadian Journal of Psychiatry. 2004;49(11):753–60.

Khudhiar NK, Saud AM. Genetic polymorphisms rs643627 in serotonin receptor gene (5-HTR2A) with schizophrenia. Iraqi Journal of Science. 2019 Dec 29;60(12):2642–8.

Paderina DZ, Boiko AS, Pozhidaev I V., Bocharova A V., Mednova IA, Fedorenko OY, et al. Genetic polymorphisms of 5-HT receptors and antipsychotic-induced metabolic dysfunction in patients with schizophrenia. J Pers Med. 2021 Mar 1;11(3).

Maslov B, Babić D, Zovko N, Margetić B, Aukst-Margetić B. IMPACT OF PSYCHOFARMACA ON THE FREQUENCY OF METABOLIC SYNDROME IN PATIENTS WITH SHIZOPHRENIA. Vol. 21. 2009.

Pandya S. Antipsychotics: uses, actions and prescribing rationale. Nurse Prescribing. 2009 Jan;7(1):23–7.

Kato MM, Currier B, Gomez CM, Hall L, Gonzalez-Blanco M. Prevalence of Metabolic Syndrome in Hispanic and Non-Hispanic Patients with Schizophrenia. Prim Care Companion CNS Disord. 2004 Apr 1;6(2).

Kuzman MR, Medved V, Bozina N, Grubišin J, Jovanovic N, Sertic J. Association study of MDR1 and 5-HT2C genetic polymorphisms and antipsychotic-induced metabolic disturbances in female patients with schizophrenia. Pharmacogenomics Journal. 2011 Feb;11(1):35–44.

Gunes A, Melkersson KI, Scordo MG, Dahl ML. Association between HTR2C and HTR2A polymorphisms and metabolic abnormalities in patients treated with olanzapine or clozapine. J Clin Psychopharmacol. 2009 Feb;29(1):65–8.

Templeman LA, Reynolds GP, Arranz B, San L. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet Genomics. 2005;15(4):195–200.

Ellingrod VL, Perry PJ, Ringold JC, Lund BC, Bever-Stille K, Fleming F, et al. Weight gain associated with the -759 C/T polymorphism of the 5HT2C receptor and olanzapine. American Journal of Medical Genetics - Neuropsychiatric Genetics. 2005 Apr 5;134 B (1):76–8.

Risselada AJ, Vehof J, Bruggeman R, Wilffert B, Cohen D, Al Hadithy AF, et al. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: A replication study. Pharmacogenomics Journal. 2012 Feb;12(1):62–7.

Downloads

Published

2024-09-15

How to Cite

1.
Zinah Abdulhameed Alobaidi, Mohammed SI. Olanzapine-induced Metabolic Syndrome and its Association with -759C>T Polymorphism of the HTR2C Gene in Iraqi Schizophrenic Patients. IJPS [Internet]. 2024 Sep. 15 [cited 2024 Sep. 27];33(3):37-46. Available from: https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/2731