J Korean Med Sci.  2006 Jun;21(3):533-538. 10.3346/jkms.2006.21.3.533.

Association between Alcoholism and the Genetic Polymorphisms of the GABA(A) Receptor Genes on Chromosome 5q33-34 in Korean Population

Affiliations
  • 1Department of Psychiatry, College of Medicine, Gyeongsang National University, Jinju, Korea. bjkim@gsnu.ac.kr
  • 2Department of Psychiatry, Changwon Hospital, Changwon, Korea.

Abstract

Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABA(A) receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABA(A) receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABA(A) alpha1 and GABA(A) alpha6 receptor gene and alcoholism. The GG genotype of the GABA(A) alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABA(A) beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABA(A) alpha1 and GABA(A) alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABA(A) alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.

Keyword

Alcoholism; Polymorphism, Genetic; GABA-A Receptor Gene

MeSH Terms

Sequence Analysis, DNA
Receptors, GABA-A/*genetics
*Polymorphism, Genetic
Models, Statistical
Middle Aged
Male
Korea
Humans
*Genetic Predisposition to Disease
DNA/metabolism
*Chromosomes, Human, Pair 5
Alcoholism/*genetics
Age of Onset
Adult

Reference

1. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Arch Gen Psychiatry. 1994. 51:8–19.
Article
2. Cloninger CR, Bohman M, Sigvardsson S. Inheritance of alcohol abuse: cross-fostering analysis of adopted men. Arch Gen Psychiatry. 1981. 38:861–868.
3. Kendler KS, Heath AC, Neale MC, Kessler RC, Eaves LJ. A population-based twin study of alcoholism in women. JAMA. 1992. 268:1877–1882.
Article
4. Dick DM, Foroud T. Candidate genes for alcohol dependence: a review of genetic evidence from human studies. Alcohol Clin Exp Res. 2003. 27:868–879.
Article
5. Buck KJ. Molecular genetic analysis of the role of GABAergic systems in the behavioral and cellular actions of alcohol. Behav Genet. 1996. 26:313–323.
Article
6. Grobin AC, Matthews DB, Devaud LL, Morrow AL. The role of GABA-A receptors in the acute and chronic effects of ethanol. Psychophamacology. 1998. 139:2–19.
7. McLean PJ, Farb DH, Russek SJ. Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster. Genomics. 1995. 26:580–586.
8. Greger V, Knoll JH, Woolf E, Glatt K, Tyndale RF, DeLorey TM, Olsen RW, Tobin AJ, Sikela JM, Nakatsu Y, et al. The gamma-aminobutyric acid receptor gamma 3 subunit gene (GABRG3) is tightly linked to the alpha 5 subunit gene (GABRA5) on human chromosome 15q11-q13 and is transcribed in the same orientation. Genomics. 1995. 26:258–264.
9. Loh EW, Ball D. Role of the GABA(A)beta2, GABA(A)alpha6, GABA (A)alpha1 and GABA(A)gamma2 receptor subunit genes cluster in drug responses and the development of alcohol dependence. Neurochem Int. 2000. 37:413–423.
10. Buck KJ, Hood HM. Genetic association of a GABA(A) receptor gamma2 subunit variant with severity of acute physiological dependence on alcohol. Mammalian Genome. 1998. 9:975–978.
11. Song J, Koller DL, Foroud T, Carr K, Zhao J, Rice J, Nurnberger JI Jr, Begleiter H, Porjesz B, Smith TL, Schuckit MA, Edenberg HJ. Association of GABA-A receptors and alcohol dependence and the effects of genetic imprinting. Am J Med Genet. 2003. 117:39–45.
Article
12. Dick DM, Edenberg HJ, Xuei X, Goate A, Hesselbrock V, Schuckit M, Crowe R, Foroud T. No association of the GABAA receptor genes on chromosome 5 with alcoholism in the collaborative study on the genetics of alcoholism sample. Am J Med Genet B Neuropsychiatr Genet. 2005. 132:24–28.
13. Loh EW, Smith I, Murray R, McLaughlin M, McNulty S, Ball D. Association between variants at the GABAAbeta2, GABAAalpha6 and GABAAgamma2 gene cluster and alcohol dependence in a Scottish population. Mol Psychiatry. 1999. 4:539–544.
14. Radel M, Vallejo RL, Iwata N, Aragon R, Long JC, Virkkunen M, Goldman D. Haplotype-based localization of an alcohol dependence gene to the 5q34 gamma-aminobutyric acid type A gene cluster. Arch Gen Psychiatry. 2005. 62:47–55.
15. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 1994. 4th edition (DSM-IV). Washington, DC: American Psychiatric Association;195–196.
16. Skinner HA, Allen BA. Alcohol dependence syndrome: measurement and validation. J Abnorm Psychol. 1982. 91:199–209.
Article
17. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An Inventory for measuring depression. Arch Gen Psychiatry. 1961. 4:561–571.
Article
18. Anton RF. Obsessive-compulsive aspects of craving: development of the Obsessive Compulsive Drinking Scale. Addiction. 2000. 95:211–217.
Article
19. Han GR, Lee YW, Lee HL, Kim SM, Ku TW, Kang IH, Lee HS, Hwang JJ. A Korean population study of the nine STR loci FGA, VWA, D3S1358, D18S51, D21S11, D8S1179, D7S820, D13S317 and D5S818. Int J Legal Med. 2000. 114:41–44.
Article
20. Schuckit MA. Sadock BJ, Sadock VA, editors. Alcohol-related disorders. Kaplan and Sadock's comprehensive textbook of psychiatry. 2004. 8th edition. Philadelphia: Lippincott Willains and Wilkins;1168–1188.
21. Sigvardsson S, Bohman M, Cloninger CR. Replication of the Stockholm Adoption Study of alcoholism: Confirmatory cross-fostering analysis. Arch Gen Psychiatry. 1996. 53:681–687.
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr