Alcoholism: Genes and mechanisms

Pharmacogenomics

Volumn 5, Issue 8, 2004, Pages 1037-1048

  Oroszi, Gabor ^a   Goldman, David ^a  

^a NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM   (United States)

Author keywords

ADH; Alcoholism; ALDH; COMT; GABAa 6; Genetics; HTTLPR; NPY; OPRM1; Treatment response

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; ALCOHOL DEHYDROGENASE; ALDEHYDE DEHYDROGENASE ISOENZYME 2; CATECHOL METHYLTRANSFERASE; CEFAMANDOLE; CEFOTETAN; CHLORPROPAMIDE; DISULFIRAM; HISTAMINE H1 RECEPTOR; HISTAMINE H2 RECEPTOR; HISTAMINE METHYLTRANSFERASE; METRONIDAZOLE; NALTREXONE; NEUROPEPTIDE Y; OPIATE RECEPTOR; SEROTONIN 3 RECEPTOR; SEROTONIN TRANSPORTER; SEROTONIN UPTAKE INHIBITOR;

ALCOHOL ABSTINENCE; ALCOHOL CONSUMPTION; ALCOHOL METABOLISM; ALCOHOLISM; ALLELE; AMINO ACID SUBSTITUTION; ANXIETY; COGNITION; DEPRESSION; DYSPHORIA; ENZYME ACTIVITY; ENZYME MECHANISM; FLUSHING; GENE CLUSTER; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HAPLOTYPE; HEREDITY; HETEROZYGOSITY; HUMAN; NERVE CELL PLASTICITY; NEUROBIOLOGY; NEUROTRANSMISSION; NUCLEOTIDE SEQUENCE; PHENOTYPE; REVIEW; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN MANIFESTATION;

ALCOHOLISM; CENTRAL NERVOUS SYSTEM DEPRESSANTS; ETHANOL; HUMANS; PHARMACOGENETICS;

PYRONIA TITHONUS;

EID: 11044219969     PISSN: 14622416     EISSN: None     Source Type: Journal    
DOI: 10.1517/14622416.5.8.1037     Document Type: Review

References (90)

1. Weisner C, Matzger H, Kaskutas LA: How important is treatment? One-year outcomes of treated and untreated alcohol-dependent individuals. Addiction 98, 901-911 (2003).
2. Goldman D, Bergen A: General and specific inheritance of substance abuse and alcoholism. Arch. Gen. Psychiatry 55, 964-965 (1998).
3. Enoch MA: Pharmacogenomics of alcohol response and addiction. Am. J. Pharmacogenomics 3, 217-232 (2003).
4. Dick DM, Foroud T: Candidate genes for alcohol dependence: a review of genetic evidence from human studies. Alcohol Clin. Exp. Res. 27, 868-879 (2003).
5. Schumann G, Spanagel R, Mann K: Candidate genes for alcohol dependence: animal studies. Alcohol Clin. Exp. Res. 27, 880-888 (2003).
6. Thomasson HR, Crabb DW, Edenberg HJ et al.: Low frequency of the ADH2*2 allele among Atayal natives of Taiwan with alcohol use disorders. Alcohol Clin. Exp. Res. 18, 640-643 (1994).
7. Schuckit MA, Smith TL: An 8-year follow-up of 450 sons of alcoholic and control subjects. Arch. Gen. Psychiatry 53, 202-210 (1996).
8. Schuckit MA, Edenberg HJ, Kalmijn J et al.: A genome-wide search for genes that relate to a low level of response to alcohol. Alcohol Clin. Exp. Res. 25, 323-329 (2001).
9. Viken RJ, Rose RJ, Morzorati SL, Christian JC, Li TK: Subjective intoxication in response to alcohol challenge: heritability and covariation with personality, breath alcohol level, and drinking history. Alcohol Clin. Exp. Res. 27, 795-803 (2003).
10. Heath AC, Madden PA. Bucholz KK et al.: Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk. Psychol. Med. 29, 1069-1081 (1999).
11. Duester G, Farres J, Felder MR et al.: Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family. Biochem. Pharmacol. 58, 389-395 (1999).
12. Chen CC, Lu RB, Chen YC et al.: Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism. Am. J. Hum. Genet. 65, 795-807 (1999).
13. Yin SJ, Chou CF, Lai CL, Lee SL, Han CL: Human class IV alcohol dehydrogenase: kinetic mechanism, functional roles and medical relevance. Chem. Biol. Interact. 143-144, 219-227 (2003).
14. McBride WJ, Li TK, Deitrich RA, Zimatkin S, Smith BR, Rodd-Henricks ZA: Involvement of acetaldehyde in alcohol addiction. Alcohol Clin. Exp. Res. 26, 114-119 (2002).
15. Forsberg L, Lyrenas L, de Faire U, Morgenstern R: A common functional C-T substitution polymorphism in the promoter region of the human catalase gene influences transcription factor binding, reporter gene transcription and is correlated to blood catalase levels. Free Radic. Biol. Med. 30, 500-505 (2001).
16. Hu X, Oroszi G, Chun J, Smith TL, Goldman D, Schuckit MA: An expanded evaluation of the relationship of four alleles to the LR to alcohol and the alcoholism risk. Alcohol. Clin. Exp. Res. (In Press).
17. Konishi T, Calvillo M, Leng AS et al.: The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men. Exp. Mol. Pathol. 74, 183-189 (2003).
18. Sun F, Tsuritani I, Yamada Y: Contribution of genetic polymorphisms in ethanol-metabolizing enzymes to problem drinking behavior in middle-aged Japanese men. Behav. Genet. 32, 229-236 (2002).
19. Eriksson CJ, Fukunaga T: Human blood acetaldehyde (update 1992). Alcohol. Alcohol Suppl. 2, 9-25 (1993).
20. Koivisto T, Kaihovaara P, Salaspuro M: Acetaldehyde induces histamine release from purified rat peritoneal mast cells. Life. Sci. 64, 183-190 (1999).
21. Anton RF: Pharmacologic approaches to the management of alcoholism. J. Clin. Psychiatry 62(Suppl. 20), 11-17 (2001).
22. Zimatkin SM, Anichtchik OV: Alcohol-histamine interactions. Alcohol. Alcohol 34, 141-147 (1999).
23. Preuss CV, Wood TC, Szumlanski CL et al.: Human histamine N-methyltransferase pharmacogenetics: common genetic polymorphisms that alter activity. Mol. Pharmacol. 53, 708-717 (1998).
24. Long JC, Knowler WC, Hanson RL et al.: Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population. Am. J. Med. Genet. 81, 216-221 (1998).
25. Reich T, Edenberg HJ, Goate A et al.: Genome-wide search for genes affecting the risk for alcohol dependence. Am. J. Med. Genet. 81, 207-215 (1998).
26. Osier MV, Pakstis AJ, Soodyall H et al.: A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity. Am. J. Hum. Genet. 71, 84-99 (2002).
27. Neumark YD, Friedlander Y, Durst R et al.: Alcohol dehydrogenase polymorphisms influence alcohol-elimination rates in a male Jewish population. Alcohol. Clin. Exp. Res. 28, 10-14 (2004).
28. Wall TL, Carr LG, Ehlers CL: Protective association of genetic variation in alcohol dehydrogenase with alcohol dependence in Native American Mission Indians. Am. J. Psychiatry 160, 41-46 (2003).
29. Osier M, Pakstis AJ, Kidd JR et al.: Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. Am. J. Hum. Genet. 64, 1147-1157 (1999).
30. Mulligan CJ, Robin RW, Osier MV et al.: Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. Hum. Genet. 113, 325-336 (2003).
31. Osier MV, Pakstis AJ, Goldman D, Edenberg HJ, Kidd JR, Kidd KK: A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans. Alcohol. Clin. Exp. Res. 26, 1759-1763 (2002).
32. Bergen AW, Kokoszka J, Peterson R et al.: μ Opioid receptor gene variants: lack of association with alcohol dependence. Mol Psychiatry 2, 490-494 (1997).
33. Bond C, LaForge KS, Tian M et al.: Single-nucleotide polymorphism in the human μ opioid receptor gene alters β -endorphin binding and activity: possible implications for opiate addiction. Proc. Natl. Acad. Sci. USA 95, 9608-9613 (1998).
34. Hernandez-Avila CA, Wand G, Luo X, Gelernter J, Kranzler HR: Association between the cortisol response to opioid blockade and the Asn40Asp polymorphism at the μ-opioid receptor locus (OPRM1). Am. J. Med. Genet. 118B, 60-65 (2003).
35. Wand GS, McCaul M, Yang X et al.: The μ-opioid receptor gene polymorphism (A118G) alters HPA axis activation induced by opioid receptor blockade. Neuropsychopharmacology 26, 106-114 (2002).
36. Oslin DW, Berrettini W, Kranzler HR et al.: A functional polymorphism of the μ-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 28, 1546-1552 (2003).
37. Lerman C, Wileyto EP, Patterson F et al.: The functional μ opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial. Pharmacogenomics J. 4(3), 184-192 (2004).
38. Marinelli PW, Quirion R, Gianoulakis C: A microdialysis profile of β-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration. Pychopharmacology (Berl. 169, 60-67 (2003).
39. Krishnan-Sarin S, Meandzija B, O'Malley S: Naltrexone and nicotine patch smoking cessation: a preliminary study. Nicotine Tob. Res. 5, 851-857 (2003).
40. True WR, Xian H, Scherrer JF et al.: Common genetic vulnerability for nicotine and alcohol dependence in men. Arch. Gen. Pychiatry 56, 655-661 (1999).
41. Lesch KP, Bengel D, Heils A et al.: Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527-1531 (1996).
42. Heinz A, Jones DW, Mazzanti C et al.: A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. Biol Psychiatry 47, 643-649 (2000).
43. Little KY, McLaughlin DP, Zhang L et al.: Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and mRNA levels. Am. J. Psychiatry 155, 207-213 (1998).
44. Hu X, Lipsky RH, Zhu G et al.: HTTLPR is triallelic, and the high expression allele predicts obsessive-compulsive disorder. Neuron. (Submitted).
45. Hariri AR, Mattay VS, Tessitore A et al.: Serotonin transporter genetic variation and the response of the human amygdala. Science 297, 400-403 (2002).
46. Caspi A, Sugden K, Moffitt TE et al.: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386-389 (2003).
47. Zanardi R, Serretti A, Rossini D et al.: Factors affecting fluvoxamine antidepressant activity- influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol. Psychiatry 50, 323-330 (2001).
48. Schuckit MA, Mazzanti C, Smith TL et al.: Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA α6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study. Biol. Psychiatry 45, 647-651 (1999).
49. Sen S, Villafuerte S, Nesse R et al.: Serotonin transporter and GABAA α6 receptor variants are associated with neuroticism. Biol. Psychiatry 55, 244-249 (2004).
50. Hammoumi S, Payen A, Favre JD et al.: Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence? Alcohol 17, 107-112 (1999).
51. Turker T, Sodmann R, Goebel U et al.: High ethanol tolerance in young adults is associated with the low-activity variant of the promoter of the human serotonin transporter gene. Neurosci. Lett. 248, 147-150 (1998).
52. Sander T, Harms H, Dufeu P et al.: Serotonin transporter gene variants in alcohol-dependent subjects with dissocial personality disorder. Biol Psychiatry 43, 908-912 (1998).
53. Hallikainen T, Saito T, Lachman HM et al.: Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior. Mol Psychiatry 4, 385-388 (1999).
54. Matsumoto M, Weickert CS, Akil M et al.: Catechol O methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function. Neuroscience 116, 127-137 (2003).
55. Mannisto PT, Kaakkola S: Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev. 51, 593-628 (1999).
56. Egan MF, Goldberg TE, Kolachana BS et al.: Effect of COMT Val 108/158Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl. Acad. Sci. USA 98, 6917-6922 (2001).
57. Enoch MA, Xu K, Ferro E, Harris CR, Goldman D: Genetic origins of anxiety in women: a role for a functional catechol-O methyltransferase polymorphism. Psychiatr. Genet. 13, 33-41 (2003).
58. Xu K. Lichtermann D, Lipsky RH et al.: A catechol-O methyltransferase haplotype is highly associated with heroin dependence in two populations. J Med Genetics (Submitted).
59. Zubieta JK, Heitzeg MM, Smith YR et al.: COMT val158met genotype affects μ-opioid neurotransmitter responses to a pain stressor. Science 299, 1240-1243 (2003).
60. Klausberger T, Fuchs K, Mayer B, Ehya N, Sieghart W: GABA(A) receptor assembly. Identification and structure of γ(2) sequences forming the intersubunit contacts with α(1) and β(3) subunits. J. Biol. Chem. 275, 8921-8928 (2000).
61. Farrar SJ, Whiting PJ, Bonnert TP, McKernan RM: Stoichiometry of a ligand-gated ion channel determined by fluorescence energy transfer. J. Biol. Chem. 274, 10100-10104 (1999).
62. Sieghart W, Fuchs K, Tretter V et al.: Structure and subunit composition of GABA(A) receptors. Neurochem. Int. 34, 379-385 (1999).
63. Grobin AC, Matthews DB, Devaud LL, Morrow AL: The role of GABA(A) receptors in die acute and chronic effects of ethanol. Psychopharmacology (Berl.) 139, 2-19 (1998).
64. Kumar S, Kralic JE, O'Buckley TK, Grobin AC, Morrow AL: Chronic ethanol consumption enhances internalization of alpha1 subunit-containing GABAA receptors in cerebral cortex. J. Neurochem. 86, 700-708 (2003).
65. Korpi ER, Kleingoor C, Kettemnann H, Seeburg PH: Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor. Nature 361, 356-359 (1993).
66. Iwata N, Cowley DS, Radel M, Roy-Byrne PP, Goldman D: Relationship between a GABAA α6 Pro385Ser substitution and benzodiazepine sensitivity. Am. J. Psychiatry 156, 1447-1449 (1999).
67. Iwata N, Virkkunen M, Goldman D: Identification of a naturally occurring Pro385-Ser385 substitution in the GABA(A) receptor α6 subunit gene in alcoholics and healthy volunteers. Mol Psychiatry 5, 316-319 (2000).
68. Edenberg HJ, Dick DM, Xuei X et al.: Variations in GABRA2, encoding the α2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am. J. Hum. Genet. 74, 705-714 (2004).
69. Kranzler H, Covault J, Gelernter J, Nellissery M: Allelic and haplorypic association of GABA α-2 gene with alcohol dependence. Alcohol Clin. Exp. Res. 28(5; Suppl.), 49A (2004).
70. Pandey SC, Carr LG, Heilig M, Ilveskoski E, Thiele TE: Neuropeptide y and alcoholism: generic, molecular, and pharmacological evidence. Alcohol. Clin. Exp. Res. 27, 149-154 (2003).
71. Thorsell A, Heilig M: Diverse functions of neuropeptide Y revealed using genetically modified animals. Neuropeptides 36, 182-193 (2002).
72. Thiele TE, Koh MT, Pedrazzini T: Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor. J. Neurosci. 22, RC208 (2002).
73. Thiele TE, Marsh DJ, Ste Marie L, Bernstein IL, Palmiter RD: Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature 396, 366-369 (1998).
74. Karvonen MK, Pesonen U, Koulu M et al.: Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels. Nat. Med. 4, 1434-1437 (1998).
75. Kallio J, Pesonen U, Kaipio K et al.: Altered intracellular processing and release of neuropeptide Y due to leucine 7 to proline 7 polymorphism in the signal peptide of preproneuropeptide Y in humans. FASEB 15, 1242-1244 (2001).
76. Karvonen MK, Valkonen VP, Lakka TA et al.: Leucine7 to proline7 polymorphism in the preproneuropeptide Y is associated with the progression of carotid atherosclerosis, blood pressure and serum lipids in Finnish men. Atherosclerosis 159, 145-151 (2001).
77. Kauhanen J, Karvonen MK, Pesonen U et al.: Neuropeptide Y polymorphism and alcohol consumption in middle-aged men. Am. J. Med. Genet. 93, 117-121 (2000).
78. Lappalainen J, Kranzler HR, Malison R et al.: A functional neuropeptide Y Leu7Pro polymorphism associated with alcohol dependence in a large population sample from the United States. Arch. Gen. Psychiatry 59, 825-831 (2002).
79. Ilveskoski E, Kajander OA, Lehtimaki T et al.: Association of neuropeptide y polymorphism with the occurrence of type 1 and type 2 alcoholism. Alcohol. Clin. Exp. Res. 25, 1420-1422 (2001).
80. Zhu G, Pollak L, Mottagui-Tabar S et al.: NPY Leu7Pro and alcohol dependence in Finnish and Swedish populations. Alcohol. Clin. Exp. Res. 27, 19-24 (2003).
81. McBride WJ, Lovinger DM, Machu T et al.: Serotonin-3 receptors in the actions of alcohol, alcohol reinforcement, and alcoholism. Alcohol. Clin. Exp. Res. 28, 257-267 (2004).
82. Lovinger DM: 5-HT3 receptors and the neural actions of alcohols: an increasingly exciting topic. Neurochem. Int. 35, 125-130 (1999).
83. Niesler B, Weiss B, Fischer C et al.: Serotonin receptor gene HTR3A variants in schizophrenic and bipolar affective patients. Pharmacogenetics 11, 21-27 (2001).
84. Kaiser R, Tremblay PB, Sezer O, Possinger K, Roots I, Brockmoller J: Investigation of the association between 5-HT3A receptor gene polymorphisms and efficiency of antiemetic treatment with 5-HT3 receptor antagonists. Pharmacogenetics 14, 271-278 (2004).
85. Tremblay PB, Kaiser R, Sezer O et al.: Variations in the 5-hydroxytryptamine type 3B receptor gene as predictors of the efficacy of antiemetic treatment in cancer patients. J. Clin. Oncol 21, 2147-2155 (2003).
86. Niesler B, Flohr T, Nothen MM et al.: Association between the 5′ UTR variant C178T of the serotonin receptor gene HTR3A and bipolar affective disorder. Pharmacogenetics 11, 471-475 (2001).
87. Johnson BA, Roache JD, Javors MA et al.: Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: a randomized controlled trial. JAMA 284, 963-971 (2000).
88. Kranzler HR, Pierucci-Lagha A, Feinn R, Hernandez-Avila C: Effects of ondansetron in early-versus late-onset alcoholics: a prospective, open-label study. Alcohol. Clin. Exp. Res. 27, 1150-1155 (2003).
89. Testing combined pharmacotherapies and behavioral interventions for alcohol dependence (the COMBINE study): a pilot feasibility study. Alcohol. Clin. Exp. Res. 27, 1123-1131 (2003).
90. Dahchour A, De Witte P: Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate. Prog. Neurobiol. 60, 343-362 (2000).