Genetic variants associated with addictive behavior in Colombian addicted and non-addicted to heroin or cocaine
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Objective: Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to the derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age, and ethnicity.
Methods: A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polymorphismof the OPRM1, DRD2, DRD4, SLC6A3, SLC6A4, ABCB1, DβH and CYP2B6 genes. For allele marker identification, mini-sequencing, and fragment multiplex PCR techniques, the ethnicity of cases and controls was analyzed with 61 AIMs.
Results: The age of onset use of heroin or coca derivatives (cocaine/crack) was 16.5±6 yrs, and 99.2% of them consume several illicit drugs. It showed that controls and addicts belong to the same ethnic group. Significant differences between addicts and controls concerning schooling, marital status, social security, family, history of substance abuse (p<0.001), Int8-VNTR SLC6A3 gene (p= 0.015), and SNP 3435C>T ABCB1 gene (p= 0.001)were found.
Conclusion: The present results indicate that the VNTR-6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1 gene are both associated with addictive behavior to heroin or cocaine.
- ABCB1 protein
- SLC6A3 protein
- heroin addiction
- cocaine addiction
- crack-cocaine.
1. United Nations Office on Drug and Crime (UNODC). World Drug Report 2011. United Nations, N. Y. Publication, Sales No. E.11.XI.10.
2. Yuferov V, Levran O, Proudnikov D, Nielsen DA, Kreek MJ. Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment. Ann NY Acad Sci. 2010; 1187: 184-207. DOI: https://doi.org/10.1111/j.1749-6632.2009.05275.x
3. Madsen HB, Brown RM, Lawrence AJ. Neuroplasticity in addiction: cellular and transcriptional perspectives. Front Mol Neurosci. 2012; 5: 99. DOI: https://doi.org/10.3389/fnmol.2012.00099
4.Le Foll B, Gallo A, Le Strat Y, Lu L, Gorwood P. Genetics of dopamine receptors and drug addiction: a comprehensive review. Behav Pharmacol. 2009; 20: 1-17. DOI: https://doi.org/10.1097/FBP.0b013e3283242f05
5. Guindalini C, Laranjeira R, Collier D, Messas G, Vallada H, Breen G. Dopamine-beta hydroxylase polymorphism and cocaine addiction. Behav Brain Funct. 2008; 4: 1. DOI: https://doi.org/10.1186/1744-9081-4-1
6.Brousse G, Vorspan F, Ksouda K, Bloch V, Peoc’h K, Laplanche JL, et al. Could the inter-individual variability in cocaine-induced psychotic effects influence the development of cocaine addiction? Towards a new pharmacogenetic approach to addictions. Med Hypotheses. 2010; 75: 600-4. DOI: https://doi.org/10.1016/j.mehy.2010.07.043
7. Chu SL, Xiao D, Wang C, Jing H. Association between 5-hydroxytryptamine transporter gene-linked polymorphic region and smoking behavior in Chinese males. Chin Med J. 2009; 122: 1365-8.
8. Levran O, O’Hara K, Peles E, Li D, Barral S, Ray B, et al. ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence. Hum Mol Genet. 2008; 17: 2219-27. DOI: https://doi.org/10.1093/hmg/ddn122
9. Zanger UM, Klein K, Saussele T, Blievernicht J, Hofmann MH, Schwab M. Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics J. 2007; 8: 743-59. DOI: https://doi.org/10.2217/14622416.8.7.743
10. Blievernicht JK, Schaeffeler E, Klein K, Eichelbaum M, Schwab M, Zanger UM. MALDI-TOF mass spectrometry for multiplex genotyping of CYP2B6 single-nucleotide polymorphisms. Clin Chem. 2007; 53: 24-33 DOI: https://doi.org/10.1373/clinchem.2006.074856
11. Finger EC, Marsh AA, Buzas B, Kamel N, Rhodes R, Vythilingham M, et al. The impact of tryptophan deletion and 5-HTTLPR genotype on passive avoidance and response reversal instrumental learning tasks. Neuropsychopharmacol. 2007; 32: 206-15. DOI: https://doi.org/10.1038/sj.npp.1301182
12. Phillips C, Salas A, Sánchez JJ, Fondevila M, Gómez-Tato A, Alvarez-Dios J, et al. Inferring ancestral origin using a single multiplex assay of ancestry-informative marker SNPs. Forensic Sci Int Genet. 2007; 1: 273-80. DOI: https://doi.org/10.1016/j.fsigen.2007.06.008
13. Falush D, Stephens M, Pritchard JK. Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics. 2003; 164: 1567-87. DOI: https://doi.org/10.1093/genetics/164.4.1567
14. Conner BT, Hellemann GS, Ritchie TL, Noble EP. Genetic, personality, and environmental predictors of drug use in adolescents. J Subst Abuse Treat. 2010; 38: 178-90. DOI: https://doi.org/10.1016/j.jsat.2009.07.004
15. Veilleux JC, Colvin PJ, Anderson J, York C, Heinz AJ. A review of opioid dependence treatment: pharmacological and psychosocial interventions to treat opioid addiction. Clin Psychol Rev. 2010; 30: 155-66. DOI: https://doi.org/10.1016/j.cpr.2009.10.006
16. Fernández-Castillo N, Ribasés M, Roncero C, Casas M, Gonzalvo B, Cormand B. Association study between the DAT1, DBH and DRD2 genes and cocaine dependence in a Spanish sample. Psychiatr Genet. 2010; 20: 317-20. DOI: https://doi.org/10.1097/YPG.0b013e32833b6320
17. Guindalini C, Howard M, Haddley K, Laranjeira R, Collier D, Ammar N, et al. A dopamine transporter gene functional variant associated with cocaine abuse in a Brazilian sample. Proc Nat Acad Sci USA. 2006; 103: 4552-7. DOI: https://doi.org/10.1073/pnas.0504789103
18. van der Zwaluw CS, Engels RCME, Buitelaar J, Verkes RJ, Franke B, Scholte RHJ. Polymorphisms in the dopamine transporter gene (SLC6A3/DAT1) and alcohol dependence in humans: a systematic review. Pharmacogenomics. 2009; 10: 853-66. DOI: https://doi.org/10.2217/pgs.09.24
19. Benyamina A, Bonhomme-Faivre L, Picard V, Sabbagh A, Richard D, Blecha L, et al. Association between ABCB1 C3435T polymorphism and increased risk of Cannabis dependence. Prog Neuropsychopharmacol Biol Psych. 2009; 33: 1270-4. DOI: https://doi.org/10.1016/j.pnpbp.2009.07.016
20. Kreek MJ, Bart G, Lilly C, Laforge KS, Nielsen DA. Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments. Pharmacol Rev. 2005; 57: 1-26. DOI: https://doi.org/10.1124/pr.57.1.1
21. Lohoff FW, Bloch PJ, Hodge R, Nall AH, Ferraro TN, Kampman KM, et al. Association analysis between polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes with cocaine dependence. Neurosci Lett. 2010; 473: 87-91. DOI: https://doi.org/10.1016/j.neulet.2010.02.021
22. McGeary J. The DRD4 exon 3 VNTR polymorphism and addiction-related phenotypes: a review. Pharmacol Biochem Behav. 2009; 93: 222-9. DOI: https://doi.org/10.1016/j.pbb.2009.03.010
23. Nikolov MA, Beltcheva O, Galabova A, Ljubenova A, Jankova E, Gergov G, et al. No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample. Drug Alcohol Depend. 2011; 117: 62-5. DOI: https://doi.org/10.1016/j.drugalcdep.2010.12.026
24. Gerra G, Zaimovic A, Garofano L, Ciusa F, Moi G, Avanzini P, et al., Perceived parenting behavior in the childhood of cocaine users: relationship with genotype and personality traits. Am J Med Genet B Neuropsychiatr Genet. 2007; 144B: 52-7. DOI: https://doi.org/10.1002/ajmg.b.30388
25. Hearon BA, Calkins AW, Halperin DM, Kathryn McHugh R, Murray HW, Otto MW. Anxiety sensitivity and illicit sedative use among opiate-dependent women and men. Am J Drug Alcohol Abuse. 2010; 37: 43-7. DOI: https://doi.org/10.3109/00952990.2010.535581
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- Carlos Isaza, Juan C. Sepúlveda Arias, Julieta Henao, Pharmacogenomics in medicine. , Colombia Medica: Vol. 40 No. 3 (2009)
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