G2Cdb::Human Disease report

Disease id
D00000162
Name
Alcoholism
Nervous system disease
yes

Genes (2)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00002098 GRIN1
glutamate receptor, ionotropic, N-methyl D-aspartate 1
Y (14573320) Single nucleotide polymorphism (SNP) Y
G00002098 GRIN1
glutamate receptor, ionotropic, N-methyl D-aspartate 1
Y (15635650) Single nucleotide polymorphism (SNP) N
G00000027 GRIN2B
glutamate receptor, ionotropic, N-methyl D-aspartate 2B
Y (14573320) Single nucleotide polymorphism (SNP) Y
G00000027 GRIN2B
glutamate receptor, ionotropic, N-methyl D-aspartate 2B
Y (15812607) Single nucleotide polymorphism (SNP) N

References

  • Polymorphisms in the NMDA subunit 2B are not associated with alcohol dependence and alcohol withdrawal-induced seizures and delirium tremens.

    Tadic A, Dahmen N, Szegedi A, Rujescu D, Giegling I, Koller G, Anghelescu I, Fehr C, Klawe C, Preuss UW, Sander T, Toliat MR, Singer P, Bondy B and Soyka M

    Dept. of Psychiatry, University of Mainz, 55131 Mainz, Germany. tadic@uni-mainz.de

    Objective: Ethanol-inhibited glutamatergic neurotransmission has been shown to mediate pathophysiological mechanisms in the development of alcoholism, including withdrawal symptoms. NMDA-receptor 2B (NR2B) is a subunit that confers a high sensitivity to ethanol-induced inhibition. Previously we had reported a lack of association between the single nucleotide polymorphism (SNP) rs1806201 in the NR2B gene (GRIN2B) and alcoholism. Shortly thereafter, an association between the polymorphism and early-onset alcoholism has been reported. One aim of the present study was to test whether the association between the GRIN2B polymorphism rs1806201 and early-onset alcoholism can be replicated in a larger sample. Moreover, we hypothesized that another genetic variation within GRIN2B (rs1806191) may have an effect in the etiology of alcoholism or withdrawal-related traits.

    Methods: We extended our original study sample to a size of 377 patients and 464 healthy volunteers and performed a replication study, including the second GRIN2B SNP. Associations between allele, genotype and haplotype frequencies of the two polymorphisms and alcoholism as well as with patients' phenotypes were investigated.

    Results: No associations were found between any of the two polymorphisms, tested individually or as haplotypes, and alcoholism, respectively withdrawal-related traits.

    Conclusion: Neither the analyzed SNPs nor any of their haplotypes likely modify susceptibility to alcohol dependence or withdrawal-related phenotypes.

    European archives of psychiatry and clinical neuroscience 2005;255;2;129-35

  • GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal.

    Rujescu D, Soyka M, Dahmen N, Preuss U, Hartmann AM, Giegling I, Koller G, Bondy B, Möller HJ and Szegedi A

    Department of Psychiatry, University of Munich, Munich, Germany. Dan.Rujescu@psy.med.uni-muenchen.de

    N-Methyl-D-aspartate (NMDA) receptors, members of the glutamate receptor channel superfamily, are generally inhibited by alcohol. The expression and alternative splicing of the obligatory NR1 subunit is altered by alcohol exposure, emphasizing the involvement of the NR1 subunit, which is coded by the GRIN1 gene, in alcohol-mediated effects. We performed an association study in patients with alcohol dependence with the GRIN1 locus. Two independent case control samples consisting of a total of 442 alcohol-dependent patients and 442 unrelated controls were included. There was no overall difference in allele or genotype frequency between patients and controls. However, the 2108A allele and A-containing genotypes were over-represented in the patients with a history of withdrawal-induced seizures when compared to healthy volunteers (allele: chi(2) = 5.412, df = 1, P = 0.020) or an independent sample of patients without a history of seizures (allele: chi(2) = 4.185, df = 1, P = 0.041). Age at onset, years of alcohol dependence, and a history of delirium tremens did not differ between genotype or allele groups. These findings support the hypothesis that the GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal. This novel finding warrants replication.

    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2005;133B;1;85-7

  • Polymorphisms in the N-methyl-D-aspartate receptor 1 and 2B subunits are associated with alcoholism-related traits.

    Wernicke C, Samochowiec J, Schmidt LG, Winterer G, Smolka M, Kucharska-Mazur J, Horodnicki J, Gallinat J and Rommelspacher H

    Department of Clinical Neurobiology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany.

    Background: This study examined the hypothesis that allelic variants of the ionotropic glutamatergic N-methyl-D-aspartate receptor (NMDAR) are associated with vulnerability to alcoholism and some related traits.

    Methods: We investigated the silent G2108A and C2664T polymorphisms of the NMDAR1 and the NMDAR2B genes, respectively. The case control study included 367 alcoholic and 335 control subjects of German origin. The family-based study comprised 81 Polish alcoholic patients and their parents using the transmission disequilibrium test.

    Results: The genotype frequencies of the NMDAR1 polymorphism differed significantly between control and alcoholic subjects. This difference was also observed in more homogenous subgroups of alcoholic subjects with vegetative withdrawal syndrome and Cloninger type 1. Patients with a history of delirium tremens or seizures during withdrawal showed a significantly increased prevalence of the A allele. Genotyping of the NMDAR2B polymorphism revealed a significantly reduced T allele in Cloninger type 2 alcoholics and in patients reporting an early onset compared with control subjects. Our family-based study for NMDAR2B, revealed a trend to a preferred transmission of the C allele by the fathers, and families with early-onset patients contributed most to this trend.

    Conclusions: These results suggest that variants in NMDAR genes are associated with alcoholism and related traits.

    Biological psychiatry 2003;54;9;922-8

Literature (3)

Pubmed - human_disease

  • Polymorphisms in the NMDA subunit 2B are not associated with alcohol dependence and alcohol withdrawal-induced seizures and delirium tremens.

    Tadic A, Dahmen N, Szegedi A, Rujescu D, Giegling I, Koller G, Anghelescu I, Fehr C, Klawe C, Preuss UW, Sander T, Toliat MR, Singer P, Bondy B and Soyka M

    Dept. of Psychiatry, University of Mainz, 55131 Mainz, Germany. tadic@uni-mainz.de

    Objective: Ethanol-inhibited glutamatergic neurotransmission has been shown to mediate pathophysiological mechanisms in the development of alcoholism, including withdrawal symptoms. NMDA-receptor 2B (NR2B) is a subunit that confers a high sensitivity to ethanol-induced inhibition. Previously we had reported a lack of association between the single nucleotide polymorphism (SNP) rs1806201 in the NR2B gene (GRIN2B) and alcoholism. Shortly thereafter, an association between the polymorphism and early-onset alcoholism has been reported. One aim of the present study was to test whether the association between the GRIN2B polymorphism rs1806201 and early-onset alcoholism can be replicated in a larger sample. Moreover, we hypothesized that another genetic variation within GRIN2B (rs1806191) may have an effect in the etiology of alcoholism or withdrawal-related traits.

    Methods: We extended our original study sample to a size of 377 patients and 464 healthy volunteers and performed a replication study, including the second GRIN2B SNP. Associations between allele, genotype and haplotype frequencies of the two polymorphisms and alcoholism as well as with patients' phenotypes were investigated.

    Results: No associations were found between any of the two polymorphisms, tested individually or as haplotypes, and alcoholism, respectively withdrawal-related traits.

    Conclusion: Neither the analyzed SNPs nor any of their haplotypes likely modify susceptibility to alcohol dependence or withdrawal-related phenotypes.

    European archives of psychiatry and clinical neuroscience 2005;255;2;129-35

  • GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal.

    Rujescu D, Soyka M, Dahmen N, Preuss U, Hartmann AM, Giegling I, Koller G, Bondy B, Möller HJ and Szegedi A

    Department of Psychiatry, University of Munich, Munich, Germany. Dan.Rujescu@psy.med.uni-muenchen.de

    N-Methyl-D-aspartate (NMDA) receptors, members of the glutamate receptor channel superfamily, are generally inhibited by alcohol. The expression and alternative splicing of the obligatory NR1 subunit is altered by alcohol exposure, emphasizing the involvement of the NR1 subunit, which is coded by the GRIN1 gene, in alcohol-mediated effects. We performed an association study in patients with alcohol dependence with the GRIN1 locus. Two independent case control samples consisting of a total of 442 alcohol-dependent patients and 442 unrelated controls were included. There was no overall difference in allele or genotype frequency between patients and controls. However, the 2108A allele and A-containing genotypes were over-represented in the patients with a history of withdrawal-induced seizures when compared to healthy volunteers (allele: chi(2) = 5.412, df = 1, P = 0.020) or an independent sample of patients without a history of seizures (allele: chi(2) = 4.185, df = 1, P = 0.041). Age at onset, years of alcohol dependence, and a history of delirium tremens did not differ between genotype or allele groups. These findings support the hypothesis that the GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal. This novel finding warrants replication.

    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2005;133B;1;85-7

Pubmed - other

  • Polymorphisms in the N-methyl-D-aspartate receptor 1 and 2B subunits are associated with alcoholism-related traits.

    Wernicke C, Samochowiec J, Schmidt LG, Winterer G, Smolka M, Kucharska-Mazur J, Horodnicki J, Gallinat J and Rommelspacher H

    Department of Clinical Neurobiology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany.

    Background: This study examined the hypothesis that allelic variants of the ionotropic glutamatergic N-methyl-D-aspartate receptor (NMDAR) are associated with vulnerability to alcoholism and some related traits.

    Methods: We investigated the silent G2108A and C2664T polymorphisms of the NMDAR1 and the NMDAR2B genes, respectively. The case control study included 367 alcoholic and 335 control subjects of German origin. The family-based study comprised 81 Polish alcoholic patients and their parents using the transmission disequilibrium test.

    Results: The genotype frequencies of the NMDAR1 polymorphism differed significantly between control and alcoholic subjects. This difference was also observed in more homogenous subgroups of alcoholic subjects with vegetative withdrawal syndrome and Cloninger type 1. Patients with a history of delirium tremens or seizures during withdrawal showed a significantly increased prevalence of the A allele. Genotyping of the NMDAR2B polymorphism revealed a significantly reduced T allele in Cloninger type 2 alcoholics and in patients reporting an early onset compared with control subjects. Our family-based study for NMDAR2B, revealed a trend to a preferred transmission of the C allele by the fathers, and families with early-onset patients contributed most to this trend.

    Conclusions: These results suggest that variants in NMDAR genes are associated with alcoholism and related traits.

    Biological psychiatry 2003;54;9;922-8

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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