OBJECTIVE: Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), may be involved in the development of alcoholism. This study examined the possible roles of the genes that code for 2 forms of GAD (GAD1 and GAD2) in the development of alcoholism. METHOD: An association study was conducted among 140 male alcoholic subjects meeting the DSM-III-R criteria for alcohol dependence and 146 controls recruited from the Han Taiwanese in community and clinical settings. Psychiatric assessment of drinking conditions was conducted using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry. The SHEsis and Haploview programs were used in statistical analyses. RESULTS: Nine single-nucleotide polymorphisms (SNPs) at the GAD1 gene were valid for further statistics. Between alcoholic subjects and controls, significant differences were found in genotype distributions of SNP1 (p=0.000), SNP2 (p=0.015), SNP4 (p=0.015), SNP5 (p=0.031), SNP6 (p=0.012), and SNP8 (p=0.004) and in allele distributions of SNP1 (p=0.001), SNP2 (p=0.009), and SNP8 (p=0.009). Permutation tests of SNP1, SNP2, and SNP8 demonstrated significant differences in allele frequencies but not in 2 major haplotype blocks. Three valid SNPs at the GAD2 gene demonstrated no associations with alcoholism. Further permutation tests in the only 1 haplotype block or individual SNPs demonstrated no significant differences. CONCLUSIONS: This is the first report indicating a possible significant role of the GAD1 gene in the development of alcohol dependence and/or the course of alcohol withdrawal and outcome of alcoholism.
OBJECTIVE:Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), may be involved in the development of alcoholism. This study examined the possible roles of the genes that code for 2 forms of GAD (GAD1 and GAD2) in the development of alcoholism. METHOD: An association study was conducted among 140 male alcoholic subjects meeting the DSM-III-R criteria for alcohol dependence and 146 controls recruited from the Han Taiwanese in community and clinical settings. Psychiatric assessment of drinking conditions was conducted using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry. The SHEsis and Haploview programs were used in statistical analyses. RESULTS: Nine single-nucleotide polymorphisms (SNPs) at the GAD1 gene were valid for further statistics. Between alcoholic subjects and controls, significant differences were found in genotype distributions of SNP1 (p=0.000), SNP2 (p=0.015), SNP4 (p=0.015), SNP5 (p=0.031), SNP6 (p=0.012), and SNP8 (p=0.004) and in allele distributions of SNP1 (p=0.001), SNP2 (p=0.009), and SNP8 (p=0.009). Permutation tests of SNP1, SNP2, and SNP8 demonstrated significant differences in allele frequencies but not in 2 major haplotype blocks. Three valid SNPs at the GAD2 gene demonstrated no associations with alcoholism. Further permutation tests in the only 1 haplotype block or individual SNPs demonstrated no significant differences. CONCLUSIONS: This is the first report indicating a possible significant role of the GAD1 gene in the development of alcohol dependence and/or the course of alcohol withdrawal and outcome of alcoholism.
Authors: Stefano Marenco; Antonina A Savostyanova; Jan Willem van der Veen; Matthew Geramita; Alexa Stern; Alan S Barnett; Bhaskar Kolachana; Eugenia Radulescu; Fengyu Zhang; Joseph H Callicott; Richard E Straub; Jun Shen; Daniel R Weinberger Journal: Neuropsychopharmacology Date: 2010-03-31 Impact factor: 7.853
Authors: Narelle K Hansell; Arpana Agrawal; John B Whitfield; Katherine I Morley; Scott D Gordon; Penelope A Lind; Michele L Pergadia; Grant W Montgomery; Pamela A F Madden; Richard D Todd; Andrew C Heath; Nicholas G Martin Journal: Alcohol Clin Exp Res Date: 2009-10-23 Impact factor: 3.455
Authors: Arpana Agrawal; Anthony L Hinrichs; Gerald Dunn; Sarah Bertelsen; Danielle M Dick; Scott F Saccone; Nancy L Saccone; Richard A Grucza; Jen C Wang; C Robert Cloninger; Howard J Edenberg; Tatiana Foroud; Victor Hesselbrock; John Kramer; Kathleen K Bucholz; Samuel Kuperman; John I Nurnberger; Bernice Porjesz; Marc A Schuckit; Alison M Goate; Laura J Bierut Journal: Drug Alcohol Depend Date: 2007-10-17 Impact factor: 4.492
Authors: O Levran; D Londono; K O'Hara; M Randesi; J Rotrosen; P Casadonte; S Linzy; J Ott; M Adelson; M J Kreek Journal: Genes Brain Behav Date: 2009-06-20 Impact factor: 3.449
Authors: Po-Hsiu Kuo; Gursharan Kalsi; Carol A Prescott; Colin A Hodgkinson; David Goldman; Jeffry Alexander; Edwin J van den Oord; Xiangning Chen; Patrick F Sullivan; Diana G Patterson; Dermot Walsh; Kenneth S Kendler; Brien P Riley Journal: Drug Alcohol Depend Date: 2008-12-25 Impact factor: 4.492