Schumann, Gunter and Johann, Monika and Frank, Josef and Preuss, Ulrich and Dahmen, Norbert and Laucht, Manfred and Rietschel, Marcella and Rujescu, Dan and Lourdusamy, Anbarasu and Clarke, Toni-Kim and Krause, Kristina and Dyer, Anne and Depner, Martin and Wellek, Stefan and Treutlein, Jens and Szegedi, Armin and Giegling, Ina and Cichon, Sven and Blomeyer, Dorothea and Heinz, Andreas and Heath, Simon and Lathrop, Mark and Wodarz, Norbert and Soyka, Michael and Spanagel, Rainer and Mann, Karl (2008) Systematic analysis of Glutamatergic neurotransmission genes in alcohol dependence and adolescent risky drinking behavior. ARCHIVES OF GENERAL PSYCHIATRY, 65 (7). pp. 826-838. ISSN 0003-990X, 1538-3636
Full text not available from this repository. (Request a copy)Abstract
Context: Glutamatergic neurotransmission is implicated in alcohol-drinking behavior in animal models. Objective: To investigate whether genetic variations in glutamatergic neurotransmission genes, which are known to alter alcohol effects in rodents, contribute to the genetic basis of alcoholism in humans. Design: Association analysis of alcohol dependence and haplotype-tagging single nucleotide polymorphisms (SNPs) covering 10 glutamatergic genes. Resequencing of functional domains of these genes identified 204 SNPs. Haplotypes with a frequency of 5% or greater could be discriminated by 21 haplotype-tagging SNPs analyzed for association in 2 independent samples of alcohol-dependent adult patients and controls as well as adolescent trios. Setting: Four university medical centers in the south of Germany. Participants: One thousand three hundred thirty-seven patients and 1555 controls (study 1: 544 patients, 553 controls; study 2: 793 patients, 1002 controls). One hundred forty-four trios of 15-year-old adolescents assessed for risky drinking behavior. Main Outcome Measures: Genotype profiles for GLAST; N-methyl-D-aspartate-receptor subunits NR1, NR2A, and NR2B; MGLUR5; NNOS; PRKG2; CAMK4; the regulatory subunit of PI3K; and CREB were analyzed for association with alcohol dependence using multivariate statistical analysis. Risky adolescent drinking was tested using the transmission disequilibrium test. Results: Analysis of study 1 revealed that NR2A and MGLUR5 have the greatest relevance for human alcohol dependence among the genes selected with odds ratios of 2.35 and 1.69, respectively. Replication analysis in study 2 confirmed an association of alcohol dependence with NR2A (odds ratio, 2.01) but showed no association with MGLUR5. Combined analysis of study 1 and study 2 exhibited a more significant association on the Cochran-Mantel-Haenszel test (P<.001) for NR2A; NR2A was associated with positive family history, early onset of alcoholism, and maximum number of drinks in adults as well as risky drinking patterns in adolescents. Conclusion: Genetic variations in NR2A have the greatest relevance for human alcohol dependence among the glutamatergic genes selected for their known alteration of alcohol effects in animal models.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NMDA-RECEPTOR; ETHANOL SENSITIVITY; NR2A SUBUNIT; MICE LACKING; FYN-KINASE; ASSOCIATION; WITHDRAWAL; ANTAGONIST; PROTEIN; PHOSPHORYLATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Oct 2020 09:13 |
| Last Modified: | 28 Oct 2020 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30635 |
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