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


CONCLUSIONS
Neither the analyzed SNPs nor any of their haplotypes likely modify susceptibility to alcohol dependence or withdrawal-related phenotypes.
Tadic
Andre
A
Dept. of Psychiatry, University of Mainz, 55131 Mainz, Germany. tadic@uni-mainz.de
Dahmen
Norbert
N
Szegedi
Armin
A
Rujescu
Dan
D
Giegling
Ina
I
Koller
Gabriele
G
Anghelescu
Ion
I
Fehr
Christoph
C
Klawe
Christoph
C
Preuss
Ullrich W
UW
Sander
Thomas
T
Toliat
Mohammad R
MR
Singer
Peter
P
Bondy
Brigitta
B
Soyka
Michael
M
D000328:Adult; D017668:Age of Onset; D000430:Alcohol Withdrawal Delirium / Q000453:epidemiology / Q000235:genetics*; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004247:DNA / Q000235:genetics; D000431:Ethanol / Q000009:adverse effects*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012640:Seizures / Q000453:epidemiology / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology / Q000235:genetics*
D002492:Central Nervous System Depressants; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D004247:DNA