The Association Between -697C>G and -997G>A polymorphism of the HTR2C Gene and the Metabolic Syndrome in Iraqi Schizophrenic Patients

Main Article Content

Zinah Abdulhameed Alobaidi
Samer Imad Mohammed

Keywords

Olanzapine, Genetic polymorphism, -697C>G , -997G>A ,Schizophrenic patients,5-hydroxytryptamine 2C receptor (HTR2C) gene

Abstract

Background: Serotonin 2C receptor (5-HT2C) antagonisms play a role in the metabolic adverse effects induced by olanzapine treatment of schizophrenic patients.
Objectives: This study aimed to determine if there is an association between the genetic polymorphisms of -697G/C and -997G>A in the promoter region of the 5-hydroxytryptamine 2C receptor (HTR2C) gene and olanzapine-induced metabolic syndrome in patients with schizophrenia.
Patients and Methods: A cross-sectional study involving 50 hospitalized patients (28 males, 22 females, mean age: 47.60 years with schizophrenia. The patients were divided into two groups according to metabolic syndrome classification criteria. Following polymerase chain reaction amplification of the extracted deoxyribonucleic acid, sequencing by the Sanger method was performed to identify the polymorphism at the HTR2C promoter region.
Results: Olanzapine significantly increases the waist circumferences and body mass index in the metabolic syndrome group (P value 0.001). The GG genotype and G allele of the -697C>G were significantly present in the metabolic syndrome group. The study failed to find any association between the genotypes of -997G>A and the tendency to have metabolic syndrome.
Conclusion: The presence of the GG genotype or G allele in the -697C>G variant was significantly associated with the metabolic syndrome group. None of the -997G>A genotypes were associated with an increased risk of developing metabolic syndrome.

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References

1. Owen MJ, Sawa A, Mortensen PB. Schizophrenia. The Lancet [Internet]. 2016 Jul;388(10039):86–97.
2. 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, $67. Psychiatric Services [Internet]. 2010 May;61(5):533–533.
3. Godlewska BR, Olajossy-Hilkesberger L, Ciwoniuk M, Olajossy M, Marmurowska-Michałowska H, Limon J, et al. Olanzapine-induced weight gain is associated with the −759C/T and −697G/C polymorphisms of the HTR2C gene. The Pharmacogenomics Journal [Internet]. 2009 May 12;9(4):234–41.
4. Wirshing DA, Jennifer A. JA, Meng LR, Ballon JS, Marder SR, Wirshing WC. The Effects of Novel Antipsychotics on Glucose and Lipid Levels. The Journal of Clinical Psychiatry [Internet]. 2002 Oct 15;63(10):856–65.
5. Mulder H, Cohen D, Scheffer H, Gispen-de Wied C, Arends J, Wilmink FW, et al. HTR2C Gene
Polymorphisms and the Metabolic Syndrome in Patients With Schizophrenia. Journal of Clinical Psychopharmacology [Internet]. 2009 Feb;29(1):16–20.
6. Mohammed SI, Abdulrazzaq MH, Gorial FI. The Effect of TNF-Alpha Gene Polymorphisms At -376 G/A, -806 C/T, and -1031 T/C on The Likelihood of Becoming a Non-Responder to Etanercept in A Sample of Iraqi Rheumatoid Arthritis Patients. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) [Internet]. 2022 Dec 24;31(2):113–28.
7. Gunes A, Melkersson KI, Scordo MG, Dahl M-L. Association Between HTR2C and HTR2A Polymorphisms and Metabolic Abnormalities in Patients Treated With Olanzapine or Clozapine. Journal of Clinical Psychopharmacology [Internet]. 2009 Feb;29(1):65–8.
8. Ma X., Maimaitirexiati T., Zhang R., Gui X., Zhang W., Xu G., Hu G. HTR2C polymorphisms, olanzapine-induced weight gain and antipsychotic-induced metabolic syndrome in schizophrenia patients: A meta-analysis. Int. J. Psychiatry Clin. Pract. 2014;18:229–242. doi: 10.3109/13651501.2014.957705. [PubMed] [CrossRef] [Google Scholar].
9. Opgen-Rhein C., Brandl E.J., Müller D.J., Neuhaus A.H., Tiwari A.K., Sander T., Dettling M. Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics. 2010;11:773–780. doi: 10.2217/pgs.10.50.
10. Munim Al-Thanoon ZA, Mahmood IH. Metabolic changes caused by first generation antipsychotic versus second generation antipsychotic in schizophrenic patients. Journal of Pharmacy Research [Internet]. 2013 Jun;7(6):468–71.
11. 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 [Internet]. 2010 Aug 1;14(2):13–21.
12. Gaebel W, Zielasek J. Schizophrenia in 2020: Trends in diagnosis and therapy. Psychiatry and Clinical Neurosciences [Internet]. 2015 Jul 1;69(11):661–73.
13. 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 [Internet]. 2006 Jan;21(1):1–6.
14. Mahmood A, Ahmed M, Mohammad J. Prevalence of metabolic syndrome in angiographically confirmed coronary artery disease. Medical Journal of Babylon [Internet]. 2018;15(4):310.
15. Daray F, Rodante D, Carosella L, Silva M, Martínez M, Fernández Busch M, et al. -759C>T Polymorphism of the HTR2C Gene is Associated with Second Generation Antipsychotic-Induced Weight Gain in Female Patients with Schizophrenia. Pharmacopsychiatry [Internet]. 2016 Jul 14;50(01):14–8.
16. Maslov B, Babić D, Zovko N. Impact Of Psychofarmaca On The Frequency Of Metabolic Syndrome In Patients With Shizophrenia. Psychiatria Danubina. 2009 Feb 24;21(1):137-.
17. Pandya S. Antipsychotics: uses, actions and prescribing rationale. Nurse Prescribing. 2009 Jan;7(1):23-7.
18. 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. The Canadian Journal of Psychiatry [Internet]. 2004 Nov;49(11):753–60.
19. Khudhiar NK, Saud AM. Genetic Polymorphisms rs643627 in Serotonin Receptor Gene (5-HTR2A) with Schizophrenia. Iraqi Journal of Science [Internet]. 2019 Dec 29;2642–8.
20. Kato MM, Currier B, Gomez CM, Hall L, Gonzalez-Blanco M. Prevalence of Metabolic Syndrome in Hispanic and Non-Hispanic Patients With Schizophrenia. The Primary Care
Companion For CNS Disorders [Internet]. 2004 Apr 1;6(2).
21. Puangpetch A, Srisawasdi P, Unaharassamee W, Jiratjintana N, Vanavanan S, Punprasit S, et al. <p>Association between polymorphisms of <em>LEP</em>,<em> LEPR</em>, <em>DRD2</em>, <em>HTR2A</em> and<em> HTR2C</em> genes and risperidone- or clozapine-induced hyperglycemia</p> Pharmacogenomics and Personalized Medicine [Internet]. 2019 Aug;Volume 12:155–66.
22. Godlewska BR, Olajossy-Hilkesberger L, Ciwoniuk M, Olajossy M, Marmurowska-Michałowska H, Limon J, Landowski J. Olanzapine-induced weight gain is associated with the− 759C/T and− 697G/C polymorphisms of the HTR2C gene. The pharmacogenomics journal. 2009 Aug;9(4):234-41.
23. Mulder H, Franke B, Beek van der AA van der-, Arends J, Wilmink FW, Scheffer H, et al. The Association Between HTR2C Gene Polymorphisms and the Metabolic Syndrome in Patients With Schizophrenia. Journal of Clinical Psychopharmacology [Internet]. 2007 Aug;27(4):338–43.
24. 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. Pharmacogenetics and Genomics [Internet]. 2005 Apr;15(4):195–200.