BACKGROUND: Significant evidence has accumulated to suggest an association between single-nucleotide polymorphisms (SNPs) in the GABRA2 gene and alcoholism. However, research has yet to show an association between these polymorphisms and the human brain's reward system function. In this study, we stratified subjects who had participated in an fMRI study of alcohol cue responses according to their genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol dependence (Edenberg et al., 2004). METHODS: Genotyping showed 13 subjects to be homozygous for the high-risk allele (AA), and 23 subjects to be heterozygous (AG). In fMRI, subjects were exposed to the aromas of their preferred alcoholic drink odors (AO), as well as to appetitive control odors (ApCO) under both alcohol intoxication and placebo control conditions. RESULTS: Homozygous AA subjects had a larger [AO > ApCO] response than did AG subjects in medial frontal cortical areas thought to code reward value. However, AG subjects had a larger [AO > ApCO] effect in the ventral tegmental area. Alcohol intoxication did not alter these group differences. CONCLUSIONS: These are the first data to suggest that GABRA2 genotype could affect the brain's responses to cues associated with alcohol.
RCT Entities:
BACKGROUND: Significant evidence has accumulated to suggest an association between single-nucleotide polymorphisms (SNPs) in the GABRA2 gene and alcoholism. However, research has yet to show an association between these polymorphisms and the human brain's reward system function. In this study, we stratified subjects who had participated in an fMRI study of alcohol cue responses according to their genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol dependence (Edenberg et al., 2004). METHODS: Genotyping showed 13 subjects to be homozygous for the high-risk allele (AA), and 23 subjects to be heterozygous (AG). In fMRI, subjects were exposed to the aromas of their preferred alcoholic drink odors (AO), as well as to appetitive control odors (ApCO) under both alcohol intoxication and placebo control conditions. RESULTS: Homozygous AA subjects had a larger [AO > ApCO] response than did AG subjects in medial frontal cortical areas thought to code reward value. However, AG subjects had a larger [AO > ApCO] effect in the ventral tegmental area. Alcohol intoxication did not alter these group differences. CONCLUSIONS: These are the first data to suggest that GABRA2 genotype could affect the brain's responses to cues associated with alcohol.
Authors: Arpana Agrawal; Howard J Edenberg; Tatiana Foroud; Laura J Bierut; Gerald Dunne; Anthony L Hinrichs; John I Nurnberger; Raymond Crowe; Samuel Kuperman; Marc A Schuckit; Henri Begleiter; Bernice Porjesz; Danielle M Dick Journal: Behav Genet Date: 2006-09 Impact factor: 2.805
Authors: Jaakko Lappalainen; Evgeny Krupitsky; Mikhail Remizov; Sofia Pchelina; Anastaisa Taraskina; Edwin Zvartau; Lucia K Somberg; Jonathan Covault; Henry R Kranzler; John H Krystal; Joel Gelernter Journal: Alcohol Clin Exp Res Date: 2005-04 Impact factor: 3.455
Authors: David A Kareken; Eric D Claus; Merav Sabri; Mario Dzemidzic; Ann E K Kosobud; Alexander J Radnovich; Dwight Hector; Vijay A Ramchandani; Sean J O'Connor; Mark Lowe; Ting-Kai Li Journal: Alcohol Clin Exp Res Date: 2004-04 Impact factor: 3.455
Authors: Jonathan Covault; Joel Gelernter; Victor Hesselbrock; Maggie Nellissery; Henry R Kranzler Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2004-08-15 Impact factor: 3.568
Authors: Veronique Bragulat; Mario Dzemidzic; Thomas Talavage; Dena Davidson; Sean J O'Connor; David A Kareken Journal: Alcohol Clin Exp Res Date: 2008-07 Impact factor: 3.455
Authors: Robert A Philibert; Tracy D Gunter; Steven R H Beach; Gene H Brody; Nancy Hollenbeck; Allan Andersen; William Adams Journal: Psychiatr Genet Date: 2009-04 Impact factor: 2.458
Authors: Thomas F Denson; Kate A Blundell; Timothy P Schofield; Mark M Schira; Ulrike M Krämer Journal: Cogn Affect Behav Neurosci Date: 2018-04 Impact factor: 3.282
Authors: Martin H Plawecki; Leah Wetherill; Victor Vitvitskiy; Ann Kosobud; Ulrich S Zimmermann; Howard J Edenberg; Sean O'Connor Journal: Alcohol Clin Exp Res Date: 2012-07-20 Impact factor: 3.455
Authors: Danielle M Dick; Arpana Agrawal; Matthew C Keller; Amy Adkins; Fazil Aliev; Scott Monroe; John K Hewitt; Kenneth S Kendler; Kenneth J Sher Journal: Perspect Psychol Sci Date: 2015-01
Authors: Jonathan Covault; Timothy Pond; Richard Feinn; Albert J Arias; Cheryl Oncken; Henry R Kranzler Journal: Psychopharmacology (Berl) Date: 2014-02-21 Impact factor: 4.530
Authors: William J A Eiler; Mario Dzemidzic; K Rose Case; Robert V Considine; David A Kareken Journal: Chemosens Percept Date: 2012-03-01 Impact factor: 1.833
Authors: Richard Lieberman; Henry R Kranzler; Pujan Joshi; Dong-Guk Shin; Jonathan Covault Journal: Alcohol Clin Exp Res Date: 2015-08-06 Impact factor: 3.455