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VOLUME 3 , ISSUE 1 ( January-March, 2020 ) > List of Articles

REVIEW ARTICLE

Genetic Polymorphism in Alcohol-dependent Genes: A Review

Umamageswari Arunachalam, Adithan Chandrasekaran

Citation Information : Arunachalam U, Chandrasekaran A. Genetic Polymorphism in Alcohol-dependent Genes: A Review. 2020; 3 (1):10-15.

DOI: 10.5005/jp-journals-10082-02260

License: CC BY-NC 4.0

Published Online: 01-08-2020

Copyright Statement:  Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.


Abstract

Alcohol dependence (AD) is a complex multifactorial disorder that poses a serious medical and sociological problem. Neurobiology of drug abuse helps us understand the genetic, cellular, and molecular mechanisms that influence transition from occasional, controlled use to loss of control in drug-seeking behavior. Elements of impulsivity and compulsivity yield a composite three-stage addiction cycle mediated by discrete neurocircuits involving the basal ganglia, extended amygdala, and prefrontal cortex. Genetic polymorphisms of the genes encoding alcohol metabolism enzymes and neurotransmitter signaling molecules in dopamine (DA) and opioid systems substantially contribute to individual variations of susceptibility to AD. The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Genetic variants of these genes result in acetaldehyde accumulation and hence have a protective effect on the risk of alcoholism. Yet another mutant variant of microsomal enzyme cytochrome P 450 2E1 c2/c2 that is found to be associated with higher transcriptional activity might play a role in the development of AD. Though functional variant 118G allele in exon1 of the μ-opioid receptor (OPRM1) gene has been associated with the development of AD, few clinical studies do not unequivocally support the association. Dopamine is an important neurotransmitter involved in reward mechanism, and the most studied genetic variant of DA D2 receptor (DRD2) gene has been found to be associated with increased AD risk.


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  1. AlcoholFactsAndStats.pdf [Internet]. [cited 2020 May 21]. Available from: https://www.niaaa.nih.gov/sites/default/files/AlcoholFactsAndStats.pdf.
  2. Eashwar VMA, Umadevi R, Gopalakrishnan S. Alcohol consumption in india- an epidemiological review. J Family Med Prim Care 2020;9(1):49–55. DOI: 10.4103/jfmpc.jfmpc_873_19.
  3. Panduro A, Ramos-Lopez O, Campollo O, Zepeda-Carrillo EA, Gonzalez-Aldaco K, Torres-Valadez R, et al. High frequency of the DRD2/ANKK1 A1 allele in mexican native amerindians and mestizos and its association with alcohol consumption. Drug and Alcohol Depend 2017;172:66–72. DOI: 10.1016/j.drugalcdep.2016.12.006.
  4. Mary anne-Enoch DG. Molecular and cellular genetics of alcohol addiction. Neuropsychopharmacol 2002. 1413–1423.
  5. Edenberg HJ, Foroud T. The genetics of alcoholism: identifying specific genes through family studies. Addict Biol 2006;11(3–4): 386–396. DOI: 10.1111/j.1369-1600.2006.00035.x.
  6. Koob GF, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science 1997;278(5335):52–58. DOI: 10.1126/science.278.5335.52.
  7. Malhotra S, Basu D, Khullar M, Ghosh A, Chugh N. Candidate genes for alcohol dependence: a genetic association study from india. Indian J Med Res 2016;144(5):689. DOI: 10.4103/ijmr.IJMR_1018_14.
  8. Cichoż-Lach H, Celiński K, Wojcierowski J, Słomka M, Lis E. Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in polish men. Braz J Med Biol Res 2010;43(3):257–261. DOI: 10.1590/S0100-879X2010007500006.
  9. Gemma S, Vichi S, Testai E. Individual susceptibility and alcohol effects: biochemical and genetic aspects. Ann Ist Super Sanita 42(1):8–16.
  10. Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ 2011;342:d636. DOI: 10.1136/bmj.d636.
  11. Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ 2011;342:d671. DOI: 10.1136/bmj.d671.
  12. Katsarou M-S, Karakonstantis K, Demertzis N, Vourakis E, Skarpathioti A, Nosyrev AE, et al. Effect of single-nucleotide polymorphisms in ADH1B, ADH4, ADH1C, OPRM1, DRD2, BDNF, and ALDH2 genes on alcohol dependence in a caucasian population. Pharmacol Res Perspect 2017;5(4):e00326. DOI: 10.1002/prp2.326.
  13. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacol 2010;35(1):217–238. DOI: 10.1038/npp.2009.110.
  14. Uhl GR, Koob GF, Cable J. The neurobiology of addiction. Ann NY Acad Sci 2019;1451(1):5–28. DOI: 10.1111/nyas.13989.
  15. Galvan A, Hare TA, Parra CE, Penn J, Voss H, Glover G, et al. Earlier development of the accumbens relative to orbitofrontal cortex might underlie risk-taking behavior in adolescents. J Neurosci 2006;26(25):6885–6892. DOI: 10.1523/JNEUROSCI.1062-06.2006.
  16. Hingson RW, Heeren T, Winter MR. Age at drinking onset and alcohol dependence: age at onset, duration, and severity. Arch Pediatr Adolesc Med 2006;160(7):739–746. DOI: 10.1001/archpedi.160.7.739.
  17. Tawa EA, Hall SD, Lohoff FW. Overview of the genetics of alcohol use disorder. Alcohol Alcohol 2016;51(5):507–514. DOI: 10.1093/alcalc/agw046.
  18. Jelski W, Szmitkowski M. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the cancer diseases. Clinica Chimica Acta 2008;395(1):1–5. DOI: 10.1016/j.cca.2008.05.001.
  19. Xue Y, Wang M, Zhong D, Tong N, Chu H, Sheng X, et al. ADH1C Ile350Val polymorphism and cancer risk: evidence from 35 case–control studies. PLoS One 2012;7(5):e37227.
  20. Edenberg HJ. The genetics of alcohol metabolism. Alcohol Res Health 2007;30(1):9.
  21. Lee S-L, Chau G-Y, Yao C-T, Wu C-W, Yin S-J. Functional assessment of human alcohol dehydrogenase family in ethanol metabolism: significance of first-pass metabolism. Alcohol Clin Exp Res 2006;30(7):1132–1142. DOI: 10.1111/j.1530-0277.2006.00139.x.
  22. Ramchandani VA, Bosron WF, Li TK. Research advances in ethanol metabolism. Pathol Biol 2001;49(9):676–682. DOI: 10.1016/S0369-8114(01)00232-2.
  23. Frezza M, di Padova C, Pozzato G, Terpin M, Baraona E, Lieber CS. High blood alcohol levels in women. the role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med 1990;322(2):95–99. DOI: 10.1056/NEJM199001113220205.
  24. Reddy BM, Reddy ANS, Nagaraja T, Reddy AG, Singh L. Single nucleotide polymorphisms of the alcohol dehydrogenase genes among the 28 caste and tribal populations of india. Int J Hum Genet 2006;6(4):309–316. DOI: 10.1080/09723757.2006.11885977.
  25. Agarwal DP. Genetic polymorphisms of alcohol metabolizing enzymes. Pathol Biol 2001;49(9):703–709. DOI: 10.1016/S0369-8114(01)00242-5.
  26. Nayak JK, Sarkar BN, Das PK, Rao VR. Genetics of alcohol use in humans: an overview. Int J Hum Genet 2008;8(1–2):181–197. DOI: 10.1080/09723757.2008.11886030.
  27. Crabb DW, Edenberg HJ, Bosron WF, Li TK. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. the inactive ALDH2(2) allele is dominant. J Clin Invest 1989;83(1):314–316. DOI: 10.1172/JCI113875.
  28. Oota H, Pakstis AJ, Bonne-Tamir B, Goldman D, Grigorenko E, Kajuna SLB, et al. The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination. Ann Hum Genet 2004;68(Pt 2):93–109. DOI: 10.1046/j.1529-8817.2003.00060.x.
  29. Peng G-S, Yin J-H, Wang M-F, Lee J-T, Hsu Y-D, Yin S-J. Alcohol sensitivity in taiwanese men with different alcohol and aldehyde dehydrogenase genotypes. J Formos Med Assoc 2002;101(11):769–774.
  30. Ghosh S, Bankura B, Ghosh S, Saha ML, Pattanayak AK, Ghatak S, et al. Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in west Bengal, india. BMC Cancer 2017;17(782):1–11. DOI: 10.1186/s12885-017-3713-7.
  31. Plemenitas A, Kastelic M, Porcelli S, Serretti A, Rus Makovec M, Kores Plesnicar B, et al. Genetic variability in CYP2E1 and catalase gene among currently and formerly alcohol-dependent male subjects. Alcohol Alcohol 2015;50(2):140–145. DOI: 10.1093/alcalc/agu088.
  32. Huang C-Y, Kao C-F, Chen C-C, Kuo P-H, Huang M-C. No association of CYP2E1 genetic polymorphisms with alcohol dependence in han taiwanese population. J Formos Med Assoc 2018;117(7):646–649. DOI: 10.1016/j.jfma.2018.03.007.
  33. Howard LA, Ahluwalia JS, Lin S-K, Sellers EM, Tyndale RF. CYP2E1*1D regulatory polymorphism: association with alcohol and nicotine dependence. Pharmacogenetics 2003;13(6):321–328. DOI: 10.1097/00008571-200306000-00003.
  34. Hu Y, Hakkola J, Oscarson M, Ingelman-Sundberg M. Structural and functional characterization of the 5′-Flanking region of the rat and human cytochrome P450 2E1 genes: identification of a polymorphic repeat in the human gene. Biochem Biophys Res Commun 1999;263(2):286–293. DOI: 10.1006/bbrc.1999.1362.
  35. Iwahashi K, Suwaki H. Ethanol metabolism, toxicity and genetic polymorphism. Addict Biol 1998;3(3):249–259. DOI: 10.1080/13556219872065.
  36. Konishi T, Calvillo M, Leng A-S, Feng J, Lee T, Lee H, et al. The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in mexican american men. Exp Mol Pathol 2003;74(2):183–189. DOI: 10.1016/S0014-4800(03)00006-6.
  37. Soya SS, Padmaja N, Adithan C. Genetic polymorphisms of CYP2E1 and GSTP1 in a south indian population—comparison with north indians, caucasians and chinese. Asian Pac J Cancer Prev 2005;6(3): 315–319.
  38. Bergen AW, Kokoszka J, Peterson R, Long JC, Virkkunen M, Linnoila M, et al. Mu opioid receptor gene variants: lack of association with alcohol dependence. Mol Psychiatry 1997;2(6):490–494. DOI: 10.1038/sj.mp.4000331.
  39. Thorsell A. The μ-opioid receptor and treatment response to naltrexone. Alcohol Alcohol 2013;48(4):402–408. DOI: 10.1093/alcalc/agt030.
  40. Tan E-C, Tan C-H, Karupathivan U, Yap EPH. Mu opioid receptor gene polymorphisms and heroin dependence in asian populations. Neuroreport 2003;14(4):569–572. DOI: 10.1097/00001756-200303240-00008.
  41. van der Zwaluw CS, van den Wildenberg E, Wiers RW, Franke B, Buitelaar J, Scholte RH, et al. Polymorphisms in the μ-opioid receptor gene (OPRM1) and the implications for alcohol dependence in humans. Pharmacogenomics 2007;8(10):1427–1436. DOI: 10.2217/14622416.8.10.1427.
  42. Bart G, Kreek MJ, Ott J, LaForge KS, Proudnikov D, Pollak L, et al. Increased attributable risk related to a functional mu-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden. Neuropsychopharmacology 2005;30(2):417–422. DOI: 10.1038/sj.npp.1300598.
  43. Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR, et al. A functional polymorphism of the μ -opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 2003;28(8):1546–1552. DOI: 10.1038/sj.npp.1300219.
  44. Chamorro A-J, Marcos M, Mirón-Canelo J-A, Pastor I, González-Sarmiento R, Laso F-J. Association of μ-opioid receptor (OPRM1) gene polymorphism with response to naltrexone in alcohol dependence: a systematic review and meta-analysis. Addict Biol 2012;17(3):505–512. DOI: 10.1111/j.1369-1600.2012.00442.x.
  45. Deb I, Chakraborty J, Gangopadhyay PK, Choudhury SR, Das S. Single-nucleotide polymorphism (A118G) in exon 1 of OPRM1 gene causes alteration in downstream signaling by mu-opioid receptor and may contribute to the genetic risk for addiction. J neurochem 2010;112(2):486–496. DOI: 10.1111/j.1471-4159.2009.06472.x.
  46. Prasad P, Ambekar A, Vaswani M. Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in indian males: a preliminary study. BMC Med Genet 2010;11(1):24. DOI: 10.1186/1471-2350-11-24.
  47. Suraj Singh H, Ghosh PK, Saraswathy KN. DRD2 and ANKK1 gene polymorphisms and alcohol dependence: a case-control study among a Mendelian population of east asian ancestry. Alcohol Alcohol 2013;48(4):409–414. DOI: 10.1093/alcalc/agt014.
  48. Sinha M, Vishwakarma N, Pradhan A, Rao IA, Ahirwar B. The role of dopamine D2 receptor polymorphism Towards susceptibility to alcohol dependence among male cases of Bilaspur district: a Preliminary study. ejbps 2017;4(12):851–857.
  49. Samochowiec J, Kucharska-Mazur J, Grzywacz A, Jabłoński M, Rommelspacher H, Samochowiec A, et al. Family-based and case-control study of DRD2, DAT, 5HTT, COMT genes polymorphisms in alcohol dependence. Neurosci Lett 2006;410(1):1–5. DOI: 10.1016/j.neulet.2006.05.005.
  50. Mayfield RD, Harris RA, Schuckit MA. Genetic factors influencing alcohol dependence: genetic factors and alcohol dependence. Br J Pharmacol 2009;154(2):275–287. DOI: 10.1038/bjp.2008.88.
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