Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal
Yıl: 2021 Cilt: 24 Sayı: 3 Sayfa Aralığı: 298 - 306 Metin Dili: İngilizce DOI: 10.5505/kpd.2021.60938 İndeks Tarihi: 09-11-2021
Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal
Öz: Objective: This study was designed to investigate thechanges in expression levels of CYP1A2, CYP2D6, CYP2E1and CYP3A4 genes in patients treated for alcohol dependence and a control group. The frequency of selectedpolymorphisms of these genes that might be a risk factorfor alcohol-dependence and may affect the treatmentsuccess is also investigated. Method: Blood sampleswere collected in the beginning and at end of treatmentfrom inpatients taking alcohol dependence treatmentand from the control group. DNA and RNA isolationwere performed. Gene expression was quantified byquantitative PCR (qPCR) and RFLP technique was used forpolymorphism studies. Results: No significant differencein the expression levels of studied genes in the patientsbefore and after the treatment and between the controlgroup was detected. However, a significant differencebetween the CYP1A2*F allele frequency in control andpatient groups was observed. For CYP2D6*4 polymorphism, heterozygous genotypes have been detected inboth patients and controls, whereas no CYP2D6*4/*4was detected in either groups, indicating expression of afunctional mRNA without reducing enzyme activity. Nosignificant difference was found between the patientand control groups in the CYP2E1 c1/c2 polymorphism.CYP3A4*V polymorphism was not detected in eithergroups. Discussion: No difference in expression levels ofstudied genes in patients before and after treatment andin the control group was detected. A significant difference in the frequency of CYP1A2*1F c.734C>A polymorphism was detected between patient and controlgroups indicating a possible role of this allele as a riskfactor for alcohol dependence.
Anahtar Kelime: Alkol yoksunluğunda sitokrom p450 CYP1A2, CYP2D6, CYP2E1 ve CYP3A4 gen ekspresyonları ve polimorfizmlerinin araştırılması
Öz: Amaç: Bu çalışma, alkol bağımlılığı tedavisi gören hastalarda ve sigara kullanmayan kontrol grubunda CYP1A2, CYP2D6, CYP2E1 ve CYP3A4 genlerinin ekspresyon düzeylerindeki değişiklikleri araştırmak için tasarlanmıştır. Ek olarak, alkol bağımlılığı için risk faktörü olabilecek ve tedavi başarısını etkileyebilecek CYP1A2, CYP2D6, CYP2E1 ve CYP3A4 gen polimorfizmlerinin allel frekanslarının karşılaştırılması hedeflenmiştir. Yöntem: Yatarak tedavi gören ve alkol bağımlılığı tedavisi alan hastalardan ve kontrol grubundan tedavi başlangıcında ve sonunda perifer kan örnekleri alınarak DNA ve RNA izolasyonu yapıldı. Gen ekspresyonu kantitatif PCR (qPCR) ile ölçüldü ve polimorfizm çalışmaları için RFLP tekniği kullanıldı. Bulgular: Hastalarda çalışılan genlerin ekspresyon düzeylerinde tedavi öncesi ve sonrası ve kontrol grubu arasında anlamlı bir farklılık saptanmadı. Diğer yandan, kontrol ve hasta gruplarında CYP1A2*F allel frekansı arasında anlamlı bir fark gözlenmiştir. CYP2D6*4 polimorfizmi için, hem hastalarda hem de kontrollerde heterozigot genotipler tespit edilirken, her iki grupta da enzim aktivitesini azaltmadan fonksiyonel bir mRNA ekspresyonunu gösteren CYP2D6*4/*4 varyasyonu tespit edilmemiştir. CYP2E1c1/c2 polimorfizminde hasta ve kontrol grupları arasında anlamlı bir fark bulunmadı. CYP3A4*V polimorfizmine ise her iki grupta da saptanmadı. Sonuç: Çalışılan genlerin tedavi öncesi ve sonrası ve kontrol grubunda ekspresyon düzeylerinde farklılık saptanmadı fakat hasta ve kontrol grupları arasında CYP1A2*1F c.734C>A polimorfizminin sıklığında anlamlı bir fark tespit edildi, bunun da bu allelin alkol bağımlılığı için bir risk faktörü olarak olası bir rolüne işaret ettiğini düşünmekteyiz.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Yenigün M. Alkol Tüketimi ve Tıp (Alcohol Consumption and Medicine) Haseki Dergisi, 2006 :3-1.
- 2. World Health Organization Regianol Office in Europe. Handbook foraction to reduce alcohol-related harm. Erişim: [www.euro.who.int/data/assets/pdf_file/0012/43320/E92820.pdf] , Erişim Tarihi:10 Aralık 2010.
- 3. Guilherme P, Homero P. The Role of Genetics in Alcohol Dependence. Rev. Bras. Psiquiatr., May 2004: vol.26 suppl.1, 54- 58.
- 4. Zhao F, Su JF, Lun SM, Hou YJ, Duan LJ, Wang NC, Shen FF, Zhang YW, Gao ZW, Li J, Du XJ, Zhou FY. Association between polymorphisms in the CYP1A1, CYP2E1 and GSTM1 genes, and smoking, alcohol and upper digestivetract carcinomas in a high-incidence area of northern China. 2019;18:1267- 1277.
- 5. Pár A, Pár G. Alcoholic liver disease: theroles of genetic-epigenetic factors and the effect of abstinence. 2019;160:524-532.
- 6. Ioannides C, Lewis DF Cytochromes P450 in thebioactivation of chemicals. Curr Top MedChem 2004:4;1767–1788.
- 7. Corchero J, Pimprale S, Kimura S, Gonzalez FJ. Organization of the CYP1A cluster on human chromosome 15: implications for gene regulation. Pharmacogenetics. 2001;11:1-6.
- 8. Karabulut HG. Farmakogenetik: Laboratuvardan Klinik Uygulamaya Türkiye Klinikleri J Med Sci 2010;30:5-15.
- 9. Eichelbaum M, Ingelman-Sundberg M, Evans WE. Pharmacogenomics and individualized drug therapy. Annu Rev Med 2006:57, 119–137.
- 10. Cai L, Yu SZ, Zhang ZF. Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle, FujianProvince World J Gastroenterol 2001;7:792-795.
- 11. Peter Guengerich F, Avadhani NG. Roles of Cytochrome P450 in Metabolism of Ethanol and Carcinogens. 2018; 1032:15- 35.
- 12. Huang CY, Kao CF, Chen CC, Kuo PH, Huang MC. No association of CYP2E1 genetic polymorphisms with alcohol dependence in Han Taiwanese population. 2018 Jul;117: 646- 649.
- 13. Scott EE, Halpert JR. Structures of cytochrome P450 3A4. Trends Biochem Sci 2005: 30: 5–7.
- 14. Inoue K, Inazawa J, Nakagawa H, Shimada T, Yazamaki H, Guengerich FP, Abe T. Assignment of the human cytochrome P450 nifedipine oxidase gene (CYP3A4) to chromosome 7 at band q22.1 by fluorescence insitu hybridization. Jpn J Hum Genet. 1992;37:133-138.
- 15. Özsoy SD. Erken ve Geç Alkol Yoksunluğunda HPA Eksen Aktivitesi, Nörosteroidler ve Bunların Agresyon Eğilimi ile İlişkisi, Tıpta Uzmanlık Tezi, Erciyes Üniversitesi Tıp Fakültesi Psikiyatri Anabilim Dalı, Kayseri 2005, 5-6.
- 16. Zhu L, He Y, Niu F, Yan M, Li J, Yuan D, Jin T. Polymorphisms of drug-metabolizingenzyme CYP2E1 in Chinese Uygur population. 2018;97: e9970.
- 17. SkadrićI., Tojković O. Defining Screening Panel Of Functional Variants of CYP1A1, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 Genes in Serbian Population. 20 December 2019.
- 18. Sılvestrı L, Sonzognı L, De Sılvestrı A. CYP Enzyme Polymorphısms and Susceptıbılıty to HCV-Related Chronıc Liver Disease and Liver Cancer Int. J. Cancer, 2003: 104, 310– 317.
- 19. Lieber CS. The Discovery of the Microsomal Ethanol Oxidizing System and Its Physiologic and Pathologic Role Drug Metabolism Reviews 2004: Vol. 36, No. 3-4, 511-529.
- 20. Mırsal H, Kalyoncu A, Pektaş Ö. İlk Kez Tedavi Gören Alkol Bağımlılarının Sosyodemografik Özellikleri ve Erken Dönem Tedavi Sonuçları Yeni Sempozyum: 2000;38:112-115.
- 21. Yenilmez ED, Tamam L, Karaytug O, Tuli A. Characterization CYP1A2, CYP2C9, CYP2C19 and CYP2D6 Polymorphisms Using HRMA in Psychiatry Patients with Schizophrenia and Bipolar Disease for Personalized Medicine. 2018;21:374-380.
- 22. Finnström N, Ask B, Dahl ML. Intra-individual variation and sex differences in gene expression of cytochromes P450 in circulating leukocytes. The Pharmacogenomics Journal. 2002: 2, 111–116.
- 23. Herken H, Aynacıoğlu Ş, Esgi K, Vırıt O. Psikiyatri Hastalarında Sitokrom P450 2D6 Yavaş ve Ultra Hızlı Metabolizör Sıklıkları Türk Psikiyatri Dergisi 2001:12;83-88.
- 24. Torres FC, Cant´u AM, Berm´udez de Le´on M, Cisneros B, Zapata-Perez O, Lopez-Carillo L, Salinas JE, Albores A. CYP1A2 Phenotype and Genotype in a Population From the Carbon if erous Region of Coahuila, Mexico Toxicology Letters 2005: 156, 331–339.
- 25. Aynacıoğlu AŞ. Psikiyatrik Hastalıkların İlaçlarla Tedavisinde Farmakogenetiğin Önemi Klinik Psikiyatri Dergisi, 2001;4:249-252.
- 26. Jarvis JP, Peter AP, Shaman JA. Consequences of CYP2D6 Copy-Number Variation for Pharmacogenomics in Psychiatry. 2019;10:432.
- 27. Maggo S, Kennedy MA, Barczyk ZA, Miller AL, Rucklidge JJ, Mulder RT, Foulds JA. Common CYP2D6, CYP2C9, and CYP2C19 Gene Variants, HealthAnxiety, and Neuroticism Are Not AssociatedWith Self-Reported Antidepressant Side Effects. 2019;10:1199.
- 28. Ulusoy G. Genetıc polymorphısms of alcohol inducible CYP2E1 in Turkish popülation.M.Sc., Department of Biochemistry 2004, 123.
- 29. Liangpunsakul S, Kolwankar D, Pinto et al. Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: A comparison with nonalcoholics Hepatology, May 2005:41;1144–1150.
- 30. Lu Y, Cederbaum AI. Cisplatin-Induced Hepatotoxicity Is Enhanced by Elevated Expression of Cytochrome P450 2E1 Toxıcologıcal Scıences. 2006;89:515–523.
- 31. Zhang F, Wang F, Chen C, Wang T, Hu J, Su R, Li X, Gu B, Tang S, Chen H, Li Y. Prediction of progression of chronic atrophic gastritis with Helicobacter pylori and poor prognosis of gastric cancer by CYP3A4. J Gastroentrol Hepatol 2020:35;425- 432
- 32. JuanWang, HongliangJi, HeleiJia and DongshengGuan. Association between CYP3A4 gene rs4646437 polymorphism and the risk of hypertension in Chinese population: a case–control study. Biosci Rep 2019:39(4);BSR20190296.
| APA | Taşçıoğlu N, Saatçi Ç, emekli r, Tuncel G, Eşel E, Dundar M (2021). Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. , 298 - 306. 10.5505/kpd.2021.60938 |
| Chicago | Taşçıoğlu Nazife,Saatçi Çetin,emekli rabia,Tuncel Gulten,Eşel Ertuğrul,Dundar Munis Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. (2021): 298 - 306. 10.5505/kpd.2021.60938 |
| MLA | Taşçıoğlu Nazife,Saatçi Çetin,emekli rabia,Tuncel Gulten,Eşel Ertuğrul,Dundar Munis Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. , 2021, ss.298 - 306. 10.5505/kpd.2021.60938 |
| AMA | Taşçıoğlu N,Saatçi Ç,emekli r,Tuncel G,Eşel E,Dundar M Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. . 2021; 298 - 306. 10.5505/kpd.2021.60938 |
| Vancouver | Taşçıoğlu N,Saatçi Ç,emekli r,Tuncel G,Eşel E,Dundar M Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. . 2021; 298 - 306. 10.5505/kpd.2021.60938 |
| IEEE | Taşçıoğlu N,Saatçi Ç,emekli r,Tuncel G,Eşel E,Dundar M "Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal." , ss.298 - 306, 2021. 10.5505/kpd.2021.60938 |
| ISNAD | Taşçıoğlu, Nazife vd. "Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal". (2021), 298-306. https://doi.org/10.5505/kpd.2021.60938 |
| APA | Taşçıoğlu N, Saatçi Ç, emekli r, Tuncel G, Eşel E, Dundar M (2021). Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. Klinik Psikiyatri Dergisi, 24(3), 298 - 306. 10.5505/kpd.2021.60938 |
| Chicago | Taşçıoğlu Nazife,Saatçi Çetin,emekli rabia,Tuncel Gulten,Eşel Ertuğrul,Dundar Munis Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. Klinik Psikiyatri Dergisi 24, no.3 (2021): 298 - 306. 10.5505/kpd.2021.60938 |
| MLA | Taşçıoğlu Nazife,Saatçi Çetin,emekli rabia,Tuncel Gulten,Eşel Ertuğrul,Dundar Munis Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. Klinik Psikiyatri Dergisi, vol.24, no.3, 2021, ss.298 - 306. 10.5505/kpd.2021.60938 |
| AMA | Taşçıoğlu N,Saatçi Ç,emekli r,Tuncel G,Eşel E,Dundar M Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. Klinik Psikiyatri Dergisi. 2021; 24(3): 298 - 306. 10.5505/kpd.2021.60938 |
| Vancouver | Taşçıoğlu N,Saatçi Ç,emekli r,Tuncel G,Eşel E,Dundar M Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal. Klinik Psikiyatri Dergisi. 2021; 24(3): 298 - 306. 10.5505/kpd.2021.60938 |
| IEEE | Taşçıoğlu N,Saatçi Ç,emekli r,Tuncel G,Eşel E,Dundar M "Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal." Klinik Psikiyatri Dergisi, 24, ss.298 - 306, 2021. 10.5505/kpd.2021.60938 |
| ISNAD | Taşçıoğlu, Nazife vd. "Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal". Klinik Psikiyatri Dergisi 24/3 (2021), 298-306. https://doi.org/10.5505/kpd.2021.60938 |
