COMT and BDNF Gene Variants Help to Predict Alcohol Consumption in Alcohol-dependent Patients

Overview

Journal J Addict Med

Specialty Psychiatry

Date 2016 Nov 30

PMID 27898499

Citations 7

Authors

Anna Klimkiewicz

Anna Mach

Andrzej Jakubczyk

Jakub Klimkiewicz

Anna Wnorowska

Maciej Kopera

Sylwia Fudalej

Margit Burmeister

Kirk Brower

Marcin Wojnar

Affiliations

Soon will be listed here.

Abstract

Background: The neurobiology of alcohol dependence (AD) involves alterations in neurotransmitters and the stress response. We hypothesized that an interaction between functional variants of dopaminergic and neurotrophic genes may influence drinking in AD.

Methods: The relationship between alcohol consumption and single-nucleotide polymorphisms, Val66Met in the brain-derived neurotrophic factor (BDNF), and Val158Met in the catechol-O-methyltransferase (COMT), was analyzed among 281 alcohol-dependent individuals.

Results: Individuals carrying both the COMT Met158Met genotype and the BDNF Val66Val genotype drank more than those with other variants of these genes (P = 0.039). Those who had a family history of AD also drank more than those without a family history (P = 0.048). Patients with both Met/Met genotype in the COMT Val158Met polymorphism and Val/Val genotype in the BDNF Val66Met polymorphism suffered from more health problems than those carrying other variants (P = 0.030) and had lower motivation to change drinking patterns (P = 0.031).

Conclusions: Patients carrying both the BDNF Val66Val and COMT Met158Met variants had higher alcohol consumption. These effects may be influenced by the effects of BDNF and COMT on dopamine responses to alcohol. Motivation-enhancing strategies might benefit the group of patients identified by genotyping in this study, and also treatment aimed at reducing alcohol consumption.

Citing Articles

Association of Brain-derived Neurotrophic Factor Polymorphisms With Alcohol Use Disorder: An Updated Meta-Analysis of Genetic Association Studies.

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Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal.

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Initial Study on COMT and DRD2 Gene Polymorphisms as Well as the Influence of Temperament and Character Trait on the Severity of Alcohol Craving in Alcohol-Dependent Patients.

Czarnecki D, Ziolkowski M, Chodkiewicz J, Dlugosz A, Feldheim J, Waszkiewicz N J Clin Med. 2021; 10(24).

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Polygenic and multi locus heritability of alcoholism: Novel therapeutic targets to overcome psychological deficits.

Blum K, Baron D, Jalali R, Modestino E, Steinberg B, Elman I J Syst Integr Neurosci. 2021; 7.

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Association of Plasma Pro-Brain-Derived Neurotrophic Factor (proBDNF)/Mature Brain-Derived Neurotrophic Factor (mBDNF) Levels with BDNF Gene Val66Met Polymorphism in Alcohol Dependence.

Mo M, Fu X, Zhang X, Zhang S, Zhang H, Wu L Med Sci Monit. 2021; 27:e930421.

PMID: 34415897 PMC: 8406813. DOI: 10.12659/MSM.930421.

References

Horowitz R, Kotler M, Shufman E, Aharoni S, Kremer I, Cohen H . Confirmation of an excess of the high enzyme activity COMT val allele in heroin addicts in a family-based haplotype relative risk study. Am J Med Genet. 2000; 96(5):599-603. View

Weinshilboum R, Otterness D, Szumlanski C . Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annu Rev Pharmacol Toxicol. 1999; 39:19-52. DOI: 10.1146/annurev.pharmtox.39.1.19. View

Egan M, Kojima M, Callicott J, Goldberg T, Kolachana B, Bertolino A . The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003; 112(2):257-69. DOI: 10.1016/s0092-8674(03)00035-7. View

Sobell L, Maisto S, Sobell M, Cooper A . Reliability of alcohol abusers' self-reports of drinking behavior. Behav Res Ther. 1979; 17(2):157-60. DOI: 10.1016/0005-7967(79)90025-1. View

Wojnar M, Brower K, Strobbe S, Ilgen M, Matsumoto H, Nowosad I . Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence. Alcohol Clin Exp Res. 2009; 33(4):693-702. PMC: 2928673. DOI: 10.1111/j.1530-0277.2008.00886.x. View

Dumontheil I, Roggeman C, Ziermans T, Peyrard-Janvid M, Matsson H, Kere J . Influence of the COMT genotype on working memory and brain activity changes during development. Biol Psychiatry. 2011; 70(3):222-9. DOI: 10.1016/j.biopsych.2011.02.027. View

Gilpin N, Koob G . Neurobiology of alcohol dependence: focus on motivational mechanisms. Alcohol Res Health. 2009; 31(3):185-95. PMC: 2770186. View

Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, Weiller E . The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1999; 59 Suppl 20:22-33;quiz 34-57. View

Vasconcelos A, Neto E, Pinto G, Yoshioka F, Motta F, Vasconcelos D . Association study of the SLC6A3 VNTR (DAT) and DRD2/ANKK1 Taq1A polymorphisms with alcohol dependence in a population from northeastern Brazil. Alcohol Clin Exp Res. 2015; 39(2):205-11. DOI: 10.1111/acer.12625. View

10.

Plemenitas A, Kastelic M, o Porcelli S, Serretti A, Dolzan V, Kores Plesnicar B . Alcohol Dependence and Genetic Variability in the Serotonin Pathway among Currently and Formerly Alcohol-Dependent Males. Neuropsychobiology. 2015; 72(1):57-64. DOI: 10.1159/000437432. View

11.

Akil M, Kolachana B, Rothmond D, Hyde T, Weinberger D, Kleinman J . Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J Neurosci. 2003; 23(6):2008-13. PMC: 6742018. View

12.

Baquet Z, Bickford P, Jones K . Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci. 2005; 25(26):6251-9. PMC: 6725062. DOI: 10.1523/JNEUROSCI.4601-04.2005. View

13.

Nedic G, Nikolac Perkovic M, Sviglin K, Muck-Seler D, Borovecki F, Pivac N . Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes. Prog Neuropsychopharmacol Biol Psychiatry. 2012; 40:193-8. DOI: 10.1016/j.pnpbp.2012.09.005. View

14.

Vandenbergh D, Rodriguez L, MILLER I, Uhl G, Lachman H . High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. Am J Med Genet. 1997; 74(4):439-42. View

15.

Hallikainen T, Saito T, Lachman H, Volavka J, Pohjalainen T, Ryynanen O . Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior. Mol Psychiatry. 1999; 4(4):385-8. DOI: 10.1038/sj.mp.4000526. View

16.

Shin S, Stewart R, Ferri C, Kim J, Shin I, Kim S . An investigation of associations between alcohol use disorder and polymorphisms on ALDH2, BDNF, 5-HTTLPR, and MTHFR genes in older Korean men. Int J Geriatr Psychiatry. 2009; 25(5):441-8. DOI: 10.1002/gps.2358. View

17.

Pivac N, Kim B, Nedic G, Joo Y, Kozaric-Kovacic D, Hong J . Ethnic differences in brain-derived neurotrophic factor Val66Met polymorphism in Croatian and Korean healthy participants. Croat Med J. 2009; 50(1):43-8. PMC: 2657559. DOI: 10.3325/cmj.2009.50.43. View

18.

Matsushita S, Kimura M, Miyakawa T, Yoshino A, Murayama M, Masaki T . Association study of brain-derived neurotrophic factor gene polymorphism and alcoholism. Alcohol Clin Exp Res. 2004; 28(11):1609-12. DOI: 10.1097/01.alc.0000145697.81741.d2. View

19.

Grzywacz A, Samochowiec A, Ciechanowicz A, Samochowiec J . Family-based study of brain-derived neurotrophic factor (BDNF) gene polymorphism in alcohol dependence. Pharmacol Rep. 2010; 62(5):938-41. DOI: 10.1016/s1734-1140(10)70354-6. View

20.

Hosak L . Role of the COMT gene Val158Met polymorphism in mental disorders: a review. Eur Psychiatry. 2007; 22(5):276-81. DOI: 10.1016/j.eurpsy.2007.02.002. View