Volume 25, Issue 3 (5-2021)                   ibj 2021, 25(3): 220-225 | Back to browse issues page

PMID: 33546554
PMCID: PMC8183388


XML Print


Abstract:  
Background: Methadone therapy is a major protocol in opioid addiction cases in many health care systems. Population-based studies have shown that in addicted people, the genetic profile affects their response to methadone therapy. Therefore, this study designed to examine the frequency of two SNPs of the CYP2B6 gene (rs3745274 and rs3211371) in addicted cases in two methadone-responders and methadone non-responders groups. Methods: A total of 199 opioid-addicted individuals and 117 unaffected control subjects were genotyped for rs3745274 and rs3211371 polymorphisms of the CYP2B6 gene using the tetra-primer amplification refractory mutation system-polymerase chain reaction. Results: Results of this study revealed the significant association of rs3745274 GG (p < 0.001; OR = 0.027; 95% CI = 0.14-0.49) and GT (p < 0.001; OR = 4.04; 95% CI = 2.26-7.21) genotypes with the risk of addiction in methadone-responders. Also, a significant association between rs3745274 GG (p < 0.001; OR = 0.28; 95% CI = 0.15-0.51) and GT (p < 0.001; OR = 5.1; 95% CI = 2.8-5.28) genotypes and addiction relapse was found in methadone non-responders. Conclusion: Based on our findings, we can conclude that rs3745274 variant of CYP2B6 gene could serve as a potential biomarker, to evaluate the prognosis of addicted people fate under treatment with methadone.
Type of Study: Short Communication | Subject: Related Fields

References
1. Degenhardt L, Whiteford HA, Ferrari AJ, Baxter AJ, Charlson FJ, Hall WD, Freedman G, Burstein R, Johns N, Engell RE, Flaxman A, Murray CJL, Vos T. Global burden of disease attributable to illicit drug use and dependence: findings from the Global Burden of Disease Study 2010. Lancet 2013; 382(9904): 1564-1574. [DOI:10.1016/S0140-6736(13)61530-5]
2. Saberi Zafarghandi MB, Jadidi M, Khalili N. Iran's activities on prevention, treatment and harm reduction of drug abuse. International journal of high risk behaviors and addiction 2015; 4(4): e22863. [DOI:10.5812/ijhrba.22863]
3. Ghane T, Zamani N, Hassanian-Moghaddam H, Beyrami A, Noroozi A. Lead poisoning outbreak among opium users in the Islamic Republic of Iran, 2016-2017. Bulletin of the World Health Organization 2018; 96(3): 165-172. [DOI:10.2471/BLT.17.196287]
4. Bevilacqua L, Goldman D. Genes and addictions. Clinical pharmacology therapeutics 2009; 85(4): 359-361. [DOI:10.1038/clpt.2009.6]
5. Sinha R. Chronic stress, drug use, and vulnerability to addiction. Annals of the New York academy of sciences 2008; 1141: 105-130. [DOI:10.1196/annals.1441.030]
6. Berrettini W. A brief review of the genetics and pharmacogenetics of opioid use disorders. Dialogues in clinical neuroscience 2017; 19(3): 229-236. [DOI:10.31887/DCNS.2017.19.3/wberrettini]
7. Kendler KS, Jacobson KC, Gardner CO, Gillespie N, Aggen SA, Prescott CA. Creating a social world: A developmental twin study of peer-group deviance. Archives of general psychiatry 2007; 64(8): 958-965. [DOI:10.1001/archpsyc.64.8.958]
8. Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson KP, Manolescu A, Thorleifsson G, Stefansson H, Ingason A, Stacey SN, Bergthorsson JT, Thorlacius S, Gudmundsson J, Jonsson T, Jakobsdottir M, Saemundsdottir J, Olafsdottir O, Gudmundsson LJ, Bjornsdottir G, Kristjansson K, Skuladottir H, Isaksson HJ, Gudbjartsson T, Jones GT, Mueller T, Gottsäter A, Flex A, Aben KKH, de Vegt F, Mulders PFA, Isla D, Vidal MJ, Asin L, Saez B, Murillo L, Blondal T, Kolbeinsson H, Stefansson JG, Hansdottir I, Runarsdottir V, Pola R, Lindblad B, van Rij AM, Dieplinger B, Haltmayer M, Mayordomo JI, Kiemeney LA, Matthiasson SE, Oskarsson H, Tyrfingsson T, Gudbjartsson DF, Gulcher JR, Jonsson S, Thorsteinsdottir U, Kong A, Stefansson K. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 2008. 452(7187):638-642. [DOI:10.1038/nature06846]
9. Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nature Genetics 2010; 42(5): 441-447. [DOI:10.1038/ng.571]
10. Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, Sulem P, Rafnar T, Esko T, Walter S, Gieger C, Rawal R, Mangino M, Prokopenko I, Mägi R, Keskitalo K, Gudjonsdottir IH, Gretarsdottir S, Stefansson H, Thompson JR, Aulchenko YS, Nelis M, Aben KK, den Heijer M, Dirksen A, Ashraf H, Soranzo N, Valdes AM, Steves C, Uitterlinden AG, Hofman A, Tönjes A, Kovacs P, Hottenga JJ, Willemsen G, Vogelzangs N, Döring A, Dahmen N, Nitz B, Pergadia ML, Saez B, De Diego V, Lezcano V, Garcia-Prats MD, Ripatti S, Perola M, Kettunen J, Hartikainen AL, Pouta A, Laitinen J, Isohanni M, Huei-Yi S, Allen M, Krestyaninova M, Hall AS, Jones GT, van Rij AM, Mueller T, Dieplinger B, Haltmayer M, Jonsson S, Matthiasson SE, Oskarsson H, Tyrfingsson T, Kiemeney LA, Mayordomo JI, Lindholt JS, Pedersen JH, Franklin WA, Wolf H, Montgomery GW, Heath AC, Martin NG, Madden PA, Giegling I, Rujescu D, Järvelin MR, Salomaa V, Stumvoll M, Spector TD, Wichmann HE, Metspalu A, Samani NJ, Penninx BW, Oostra BA, Boomsma DI, Tiemeier H, van Duijn CM, Kaprio J, Gulcher JR; ENGAGE Consortium, McCarthy MI, Peltonen L, Thorsteinsdottir U, Stefansson K. Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nature genetics 2010; 42(5): 448-453. [DOI:10.1038/ng.573]
11. Bart G, Heilig M, LaForge KS, Pollak L, Leal SM, Ott J, Kreek MJ. Substantial attributable risk related to a functional mu-opioid receptor gene polymorphism in association with heroin addiction in central Sweden. Molecular psychiatry 2004; 9(6): 547-549. [DOI:10.1038/sj.mp.4001504]
12. Kreek MJ, Levran O, Reed B, Schlussman SD, Zhou Y, Butelman ER. Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics. Journal of clinical investigation 2012; 122(10): 3387-3393. [DOI:10.1172/JCI60390]
13. Maréchal JD, Kemp CA, Roberts GC, Paine MJ, Wolf CR, Sutcliffe MJ. Insights into drug metabolism by cytochromes P450 from modelling studies of CYP2D6-drug interactions. British journal of pharmacology 2008; 153 Suppl 1(Suppl 1): S82-S89. [DOI:10.1038/sj.bjp.0707570]
14. Levran O, Peles E, Hamon S, Randesi M, Adelson M, Kreek MJ. CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction. Addiction biology 2013; 18(4): 709-716. [DOI:10.1111/j.1369-1600.2011.00349.x]
15. Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug metabolism reviews 2009; 41(2): 89-295. [DOI:10.1080/03602530902843483]
16. Somogyi AA, Barratt DT, Ali RL, Coller JK. Pharmacogenomics of methadone maintenance treatment. Pharmacogenomics 2014; 15(7): 1007-1027. [DOI:10.2217/pgs.14.56]
17. National Center for Biotechnology Information. PubChem Compound Summary for CID 4095, Methadone. Reterieved from: https://pubchem.ncbi.nlm. nih.gov/compound/Methadone.
18. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic acids research 1988; 16(3):1215. [DOI:10.1093/nar/16.3.1215]
19. Ye S, Dhillon S, Ke X, Collins AR, Day IN. An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic acids research 2001; 29(17): E88. [DOI:10.1093/nar/29.17.e88]
20. Bart G. Maintenance medication for opiate addiction: the foundation of recovery. Journal of addictive diseases 2012; 31(3): 207-225. [DOI:10.1080/10550887.2012.694598]
21. Naji L, Dennis BB, Bawor M, Plater C, Pare G, Worster A, Varenbut M, Daiter J, Marsh DC, Desai D, Thabane L, Samaan Z. A prospective study to investigate predictors of relapse among patients with opioid use disorder treated with methadone. Substance abuse 2016; 10: 9-18. [DOI:10.4137/SART.S37030]
22. Victorri-Vigneau C, Verstuyft C, Bouquié R, Laforgue EJ, Hardouin JB, Leboucher J, Le Geay B, Dano C, Challet-Bouju G, Grall-Bronnec M. Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study. British journal of clinical pharmacology 2019; 85(7): 1538-1543. [DOI:10.1111/bcp.13936]
23. Talal AH, Ding Y, Venuto CS, Chakan LM, McLeod A, Dharia A, Morse GD, Brown LS, Markatou M, Kharasch ED. Toward precision prescribing for methadone: Determinants of methadone deposition. PLoS one 2020; 15(4): e0231467. [DOI:10.1371/journal.pone.0231467]
24. Chiang YC, Wang RY, Huang CL, Chen SH, Ho WJ, Lane HY, Ho IK, Yang HT, Ma WL. Reduced dosing and liability in methadone maintenance treatment by targeting oestrogen signal for morphine addiction. Journal of vellular and molecular medicine 2017; 21(12): 3552-3564. [DOI:10.1111/jcmm.13266]
25. Kharasch ED, Regina KJ, Blood J, Friedel C. Methadone pharmacogenetics: CYP2B6 polymorphisms determine plasma concentrations, clearance, and metabolism. Anesthesiology 2015; 123(5):1142-1153. [DOI:10.1097/ALN.0000000000000867]
26. Gadel S, Friedel C, Kharasch ED. Differences in methadone metabolism by CYP2B6 variants. Drug metabolism and disposition 2015; 43(7): 994-1001. [DOI:10.1124/dmd.115.064352]
27. Amunugama HT, Zhang H, Hollenberg PF. Mechanism-based inactivation of cytochrome P450 2B6 by methadone through destruction of prosthetic heme. Drug metabolism and disposition 2012; 40(9): 1765-1770. [DOI:10.1124/dmd.112.045971]
28. Zubiaur P, Saiz-Rodríguez M, Ochoa D, Belmonte C, Román M, Mejía G, Martín-Vilchez S, Abad-Santos F. Influence of CYP2B6 activity score on the pharmacokinetics and safety of single dose efavirenz in healthy volunteers. Pharmacogenomics 2020. 20(2): 235-245. [DOI:10.1038/s41397-019-0103-3]
29. Crocco P, Montesanto A, Dato S, Geracitano S, Iannone F, Passarino G, Rose G. Inter-individual variability in xenobiotic-metabolizing enzymes: implications for human aging and longevity. Genes (Basel) 201; 10(5): 403. [DOI:10.3390/genes10050403]
30. Chang JL, Lee SA, Tsai AC, Musinguzi N, Muzoora C, Bwana B, Boum Y 2nd, Haberer JE, Hunt PW, Martin J, Bangsberg DR, Kroetz DL, Siedner MJ. CYP2B6 genetic polymorphisms, depression, and viral suppression in adults living with HIV initiating Efavirenz-Containing Antiretroviral Therapy Regimens in Uganda: pooled analysis of two prospective studies. AIDS research human retroviruses 2018; 34(11):982-992. [DOI:10.1089/aid.2018.0062]
31. Ahmad T, Sabet S, Primerano DA, Richards-Waugh LL, Rankin GO. Tell-Tale SNPs: The role of CYP2B6 in methadone fatalities. Journal of analytical toxicology 2017; 41(4): 325-333. [DOI:10.1093/jat/bkw135]