Role of CYP3A4*1B gene variant in substance use disorder

Background and objective: This study aims to find out the possible association between the CYP3A4*1B gene variant (rs2740574) and substance use disorder susceptibility in the Turkish population. Materials and methods: 158 patients with substance use disorder and 100 healthy individuals matched for gender, age, and ethnicity were enrolled in the study. Genotyping was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using the MboII restriction endonuclease. The association between the CYP3A4*1B variant and substance use disorder was analyzed by using SPSS 21 and de-Finetti program. Results: CYP3A4 gene (MboII gene variant in 5’ promoter region) genotype distributions of substance use disorder patients were not significantly different from healthy controls. When the substance use and control groups were compared in terms of allele frequency, increased G allele frequency was observed in CYP3A4 variants in the substance use group (p: 0,042). Conclusion: This is the first study that investigates the association between the MboII gene variant in CYP3A4 gene 5’promoter region and substance use disorder in the literature. It was demonstrated that an increased G allele existed in Turkish substance use disorder patients. It also was planned to research the other variants of the CYP3A4 gene in the future.

Role of CYP3A4*1B Gene Variant In Substance Use Disorder

Objective: This study aims to find out the possible association between the CYP3A4*1B gene variant (rs2740574) and substance use disorder susceptibility in the Turkish population. Materials and Methods: 158 patients with substance use disorder and 100 healthy individuals matched for gender, age, and ethnicity were enrolled in the study. Genotyping was analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using the MboII restriction endonuclease. The association between the CYP3A4*1B variant and substance use disorder was analyzed using SPSS 21 and de-Finetti program. Results: The CYP3A4 gene (MboII gene variant in 5’ promoter region) genotype distributions of substance use disorder patients were not significantly different from the healthy controls. When the substance use and control groups were compared in terms of allele frequency, increased G allele frequency was observed in CYP3A4 variants in the substance use group (p: 0,042). Conclusion: This is the first study that investigates the association between the MboII gene variant in CYP3A4 gene 5’promoter region and substance use disorder in the literature. It was demonstrated that an increased G allele existed in Turkish substance use disorder patients. Plans have been made to research the other variants of the CYP3A4 gene in the future.

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  • 1. Substance abuse. World Health Organization. https://www.who.int/topics/substance_abuse/ en/ (Accessed January 17, 2019)
  • 2. Volkow ND, Koob GF, Mclellan AT. Neurobiologic Advances from the Brain Disease Model of Addiction. N Engl J Med 2016;374(4):363-71.
  • 3. World Drug Report 2018 http://www.unodc. org/wdr2018/prelaunch/WDR18_Booklet_1_ EXSUM.pdf (Accessed January 17, 2019)
  • 4. Werk AN, Cascorbi I. Functional Gene Variants of CYP3A4. Clin Pharmacol Ther 2014;96(3):340-8.
  • 5. McDonnell AM, Dang CH. Basic review of the cytochrome p450 system. J Adv Pract Oncol 2013;4(4):263-8.
  • 6. Chen L, Prasad GVR. CYP3A5 polymorphisms in renal transplant recipients: influence on tacrolimus treatment. Curr Pharmacogenomics Person Med 2018;11:23-33.
  • 7. Qin S, Liu D, Kohli M, Wang L, Vedell PT et al. TSPYL Family Regulates CYP17A1 and CYP3A4 Expression: Potential Mechanism Contributing to Abiraterone Response in Metastatic Castration-Resistant Prostate Cancer. Clin Pharmacol Ther. 2017;104(1):201-10.
  • 8. Keshava C. CYP3A4 Polymorphisms--Potential Risk Factors for Breast and Prostate Cancer: A HuGE Review. Am J Epidemiol. 2004;160(9):825- 41.
  • 9. Uçkun Z, Baskak B, Özdemir H, Özel-Kızıl E, Devrimci-Özgüven H et al. Genotype and Allele Frequency of CYP3A4 -392A>G in Turkish Patients with Major Depressive Disorder. Turk J of Pharm Sci 2018;15(2):200-06.
  • 10. Cavalli SA, Hirata MH, Hirata RD. Detection of MboII polymorphism at the 5’ promoter region of CYP3A4. Clin Chem 2001;47:348-51.
  • 11. Veiga MG, Felizi RT, Reis DG, Carelli Filho I, Fernandes CE et al. The Influence of CYP3A4 Polymorphism in Sex Steroids as a Risk Factor for Breast Cancer. Rev Bras Ginecol Obstet 2018;40(11):699-704. 12. Mitoprot. https://ihg.gsf.de/cgi-bin/hw/hwa1.pl (Accessed January 17, 2019)
  • 13. Klein K, Zanger UM. Pharmacogenomics of Cytochrome P450 3A4: Recent Progress Toward the “Missing Heritability” Problem. Front Genet 2013;4:12.
  • 14. Kiss Á, Menus Á, Tóth K, Déri M, Sirok D et al. Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure. Eur Arch Psychiatry Clin Neurosci 2019. 2020;270(1):71- 82.
  • 15. Pearce CL, Near AM, Van Den Berg DJ, Ramus SJ, Gentry-Maharaj A et al. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium. Br J Cancer. 2009;100(2):412-20.
  • 16. Bangsi D, Zhou J, Sun Y, Patel NP, Darga LL et al. Impact of a genetic variant in CYP3A4 on risk and clinical presentation of prostate cancer among white and African-American men. Urol Oncol 2006;24(1):21-7.
  • 17. Rosales A, Alvear M, Cuevas A, Saavedra N, Zambrano T et al. Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia. Clinica Chimica Acta. 2012;413(3-4):495-501.
  • 18. Tavira B, Coto E, Díaz-Corte C, Ortega F, Arias M et al. Pharmacogenetics of tacrolimus after renal transplantation: analysis of polymorphisms in genes encoding 16 drug metabolizing enzymes. Clin Chem Lab Med 2011;49(5):825-33.
Sağlık Bilimlerinde İleri Araştırmalar Dergisi-Cover
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2018
  • Yayıncı: İstanbul Üniversitesi
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