No association between dopamine D2 receptor (DRD2) alleles and crack/cocaine dependence in Brazilians
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Abstract
Introduction: The causal mechanisms behind crack/cocaine use are still unknown, but genetic influences are suggested. Objective: To investigate the relationship between the genetic polymorphism TaqI (rs1800497) in the dopamine D2 receptor (DRD2) gene and susceptibility to crack/cocaine dependence in a group of addicts to crack/cocaine and a non-addicted group. Methods: The case group (n=515) was composed of crack/cocaine-dependent men and the control group (n=106) comprised men who were considered not dependent on crack/cocaine. The oral hygiene habits, decayed, missing, and filled teeth index, gingival index, and plaque index were evaluated. The reference single nucleotide polymorphism (rs1800497 C/T) of the DRD2 gene was genotyped by a real-time polymerase chain reaction technique. Student’s t-tests for independent samples or the non-parametric Mann-Whitney test were used to compare groups regarding quantitative variables. Results: The case group showed a mean time of 9.91±7.03 years of crack use, and 61.06±92.96 stones/week. The socio-demographic profile of the sample was White, single men, with basic education, blue-collar worker, smoker, and reporting alcohol use. There was a high frequency of gingival inflammation, plaque accumulation, and caries experience. For all genetic models tested, there was no significant difference in the genotypic frequency in rs1800497 of the DRD2 gene, between case and control groups (p>0.05). Conclusion: The genetic variant in the DRD2 did not increase the vulnerability to develop crack/cocaine dependence. The complex genetic nature of crack/cocaine dependence and a large variation of DRD2 allele frequencies, depending on the population group sampled, could be one explanation for the no association.
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United Nations Office on Drugs and Crime (UNODC). World drug report: 2014. Vienna: United Nations, 2014.
Instituto Brasileiro de Geografia e Estatística (IBGE). Sidra. Available from: https://sidra.ibge.gov.br/tabela/3705
Abdalla RR, Madruga CS, Ribeiro MIP, Caetano R, Laranjeira R. Prevalence of cocaine use in Brazil: data from the II Brazilian National Alcohol and Drugs Survey (BNADS). Addict Behav. 2014;39(1):297-301. http://doi.org/10.1016/j.addbeh.2013.10.019
Waaktaar T, Kan K, Torgersen S. The genetic and environmental architecture of substance use development from early adolescence into young adulthood: a longitudinal twin study of comorbidity of alcohol, tobacco, and illicit drug use. Addiction. 2018;113(4):740-8. http://doi.org/10.1111/add.14076
Nestler EJ, Malenka RC. The addicted brain. Sci Am. 2004;290(3):78-85. http://doi.org/10.1038/scientificamerican0304-78
Agrawal A, Lynskey MT. Are there genetic influences on addiction: evidence from family, adoption and twin studies? Addiction. 2008;103(7):1069-81. http://doi.org/10.1111/j.1360-0443.2008.02213
Koob GF, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science. 1997;278(5335):52-8. http://doi.org/10.1126/science.278.5335.52
Dackis CA, O'Brien CP. Cocaine dependence: a disease of the brain's reward centers. J Subst Abuse Treat. 2001;21(3):111-17. http://doi.org/10.1016/s0740-5472(01)00192-1
Lambert G, Karila L, Lowenstein W. Neuroimaging and cocaine: mapping dependence?. Presse Med. 2008;37(4 Pt 2):679-88. http://doi.org/10.1016/j.lpm.2007.08.014
Vereczkei A, Demetrovics Z, Szekely A, Sarkozy P, Antal P, Szilagyi A, et al. Multivariate analysis of dopaminergic gene variants as risk factors of heroin dependence. PLoS One. 2013;8(6):66592. http://doi.org/10.1371/journal.pone.0066592
Ponce G, Pérez-González R, Aragüés M, Palomo T, Rodríguez-Jiménez R, Jiménez-Arriero MA, et al. The ANKK1 kinase gene and psychiatric disorders. Neurotox Res. 2009;16(1):50-9. http://doi.org/10.1007/s12640-009-9046-9
Huang Y, Ren HT, Zou Q, Wang YQ, Zhang JL, Yu XL. Computational identification and characterization of miRNAs and their target genes from five A1 Cyprinidae fishes. Saudi J Biol Sci. 2017;24(6):1126-35. http://doi.org/10.1016/j.sjbs.2015.05.007
Noble EP, Blum K, Khalsa ME, Ritchie T, Montgomery A, Wood RC, et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend. 1993 Oct;33(3):271-85. http://doi.org/10.1016/0376-8716(93)90113-5
Gelernter J, Kranzler H, Satel SL. No association between D2 dopamine receptor (DRD2) alleles or haplotypes and cocaine dependence or severity of cocaine dependence in Europeans and African-Americans. Biol Psychiatry. 1999;45(3):340-5. http://doi.org/10.1016/s0006-3223(97)00537-4
Messas G, Meira-Lima I, Turchi M, Franco O, Guindalini C, Castelo A, et al. Association study of dopamine D2 and D3 receptor gene polymorphisms with cocaine dependence. Psychiatr Genet. 2005;15(3):171-4. http://doi.org/10.1097/00041444-200509000-00006
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(2):87-91. http://doi.org/10.1016/j.neulet.2010.02.021
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 N Y Acad Sci. 2010;1187:184-207. http://doi.org/10.1111/j.1749-6632.2009.05275
Persico AM, Bird G, Gabbay FH, Uhl GR. D2 dopamine receptor gene TaqI A1 and B1 restriction fragment length polymorphisms: enhanced frequencies in psychostimulant-preferring polysubstance abusers. Biol Psychiatry. 1996;40(8):776-84. http://doi.org/10.1016/0006-3223(95)00483-1
Smith L, Watson M, Gates S, Ball D, Foxcroft D. Meta-analysis of the association of the Taq1A polymorphism with the risk of alcohol dependency: a HuGE gene-disease association review. Am J Epidemiol. 2008;167(2):125-38. http://doi.org/10.1093/aje/kwm281
WHO ASSIST Working Group. The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST): development, reliability, and feasibility. Addiction. 2002;97(9):1183-94. http://doi.org/10.1046/j.1360-0443.2002.00185.x
Albini MB, Couto ACF, Invernici MM, Martins MC, Lima AAS, Gabardo MCL, et al. Socio-demographic profile and oral health status of drug users in two municipalities of the State of Paraná, Brazil. Rev Odontol UNESP. 2015; 44:244-9. https://doi.org/10.1590/1807-2577.1068
Fernàndez-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(6):317-20. https://doi.org/10.1097/YPG.0b013e32833b6320
Isaza C, Henao J, Beltrán L, Porras L, Gonazalez M, Cruz R, et al. Genetic variants associated with addictive behavior in Colombian addicted and non-addicted to heroin or cocaine. Colomb Med (Cali). 2013;44(1):19-25.
Powledge TM. Addiction and the brain: The dopamine pathway is helping researchers find their way through the addiction maze. BioScience. 1999;49(7):513-19. https://doi.org/10.2307/1313471
Comings DE, Blum K. Reward deficiency syndrome: genetic aspects of behavioral disorders. Prog Brain Res. 2000;126:325-41. https://doi.org/10.1016/S0079-6123(00)26022-6
Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet. 2001;29(3):306-9. https://doi.org/10.1038/ng749
Gelernter J, Goldman D, Risch N. The Al allele at the D2 dopamine receptor gene and alcoholism: a reappraisal. J Am Med Assoc. 1993;269(13):1673-7.
Noble EP, Blum K. Alcoholism and the D2 dopamine receptor gene. JAMA. 1993;270(13):1547. https://doi.org/10.1001/jama.1993.03510130053027
Guindalini C, Vallada H, Breen B, Laranjeira R. Concurrent crack and powder cocaine users from Sao Paulo: do they represent a different group? BMC Public Health. 2006;6:10. https://doi.org/10.1186/1471-2458-6-10
Duailibi LB, Ribeiro M, Laranjeira R. Profile of cocaine and crack users in Brazil. Cad Saude Publica. 2008;24(Suppl 4):545-57. https://doi.org/10.1590/s0102-311x2008001600007
Miguel AQC, Madruga CS, Cogo-Moreira H, Yamauchi R, Simões V, Silva CJ, et al. Sociodemographic characteristics, patterns of crack use, concomitant substance use disorders, and psychiatric symptomatology in treatment-seeking crack-dependent individuals in Brazil. J Psychoactive Drugs. 2018;50(4):367-72. https://doi.org/10.1080/02791072.2018.1436729
D’Amore MM, Cheng DM, Kressin NR, Jones J, Samet JH, Winter M, et al. Oral health of substance-dependent individuals: impact of specific substances. J Subst Abuse Treat. 2011;41(2):179-85. https://doi.org/10.1016/j.jsat.2011.02.005
Cury PR, Oliveira MG, de Andrade KM, de Freitas MD, Dos Santos JN. Dental health status in crack/cocaine-addicted men: a cross-sectional study. Environ Sci Pollut Res Int. 2017;24(8):7585-90. https://doi.org/10.1007/s11356-017-8404-z
Sordi MB, Massochin RC, Camargo AR, Lemos T, Munhoz EA. Oral health assessment for users of marijuana and cocaine/crack substances. Braz Oral Res. 2017;31:102. https://doi.org/10.1590/1807-3107BOR-2017.vol31.0102
Goldman D, Brown GL, Albaugh B, Robin R, Goodson S, Trunzo M, et al. DRD2 dopamine receptor genotype, linkage disequilibrium, and alcoholism in American Indians and other populations. Alcohol Clin Exp Res. 1993;17(2):199-204. https://doi.org/10.1590/1807-3107BOR-2017.vol31.0102
Castiglione CM, Deinard AS, Speed WC, Sirugo G, Rosenbaum HC, Zhang Y, et al. Evolution of haplotypes at the DRD2 locus. Am J Hum Genet. 1995;57(6):1445-56.