Effect of genotype on glutamate-NMDA receptor subunit expression in caucasian alcohol misusers

Dodd, P. R., Ridge, J. P., Innes, D. J. and Tannenberg, R. K. (2008). Effect of genotype on glutamate-NMDA receptor subunit expression in caucasian alcohol misusers. In: Alcoholism: Clinical and Experimental Research. Proceedings of: Joint Scientific Meeting of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism June 27 July 2, 2008 Washington, D.C. 2008 Joint Scientific Meeting of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism, Washington, D.C., (17A-17A). 27 June-2 July 2008. doi:10.1111/j.1530-0277.2008.00685.x-i1


Author Dodd, P. R.
Ridge, J. P.
Innes, D. J.
Tannenberg, R. K.
Title of paper Effect of genotype on glutamate-NMDA receptor subunit expression in caucasian alcohol misusers
Conference name 2008 Joint Scientific Meeting of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism
Conference location Washington, D.C.
Conference dates 27 June-2 July 2008
Proceedings title Alcoholism: Clinical and Experimental Research. Proceedings of: Joint Scientific Meeting of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism June 27 July 2, 2008 Washington, D.C   Check publisher's open access policy
Place of Publication Maryland, USA
Publisher Wiley-Blackwell Publishing
Publication Year 2008
DOI 10.1111/j.1530-0277.2008.00685.x-i1
ISSN 0145-6008
1530-0277
Volume 32
Issue Supp.1
Start page 17A
End page 17A
Total pages 1
Language eng
Formatted Abstract/Summary
Alcohol misuse and dependence have a high degree of heritability, perhaps as high as 50–60%. Alcoholics differ in strength of craving, compulsion to drink, quantity of alcohol consumed (lifetime, or on the most recent drinking occasion), severity of withdrawal symptoms, propensity to become dependent on alcohol, and in the extent of brain damage they suffer. Genetic control of neurotransmitter receptor subunit composition in the brain may contribute to many of these effects.

A major brain target for ethanol is the N-methyl-Daspartate glutamate receptor (GluRNMDA), where it acts as a modulator. The receptor is a multi-subunit complex; subunit composition dictates receptor pharmacology, including responsiveness to ethanol. Persistent alcohol misuse may promote subunit switching, leading to altered receptor functionality. Using quantitative Real Time RT-PCR we determined the relative abundances of mRNA transcripts for GluRNMDA NR1, NR2A and NR2B subunits the in both superior frontal cortex (SFC), which is relatively susceptible to alcohol-mediated damage, and primary motor cortex (PMC), which is relatively spared. In alcoholics without comorbid disease, subunit transcript expression levels in both brain areas were closely comparable to those in controls. In contrast, levels of expression of all three subunits were significantly lower in both brain areas in cirrhotic alcoholics. Expression levels also differed between male and female subjects. We then studied the influence of genotype on these parameters. Subunit transcript expression differed between SFC and PMC when cirrhotic alcoholic cases were partitioned according to 5HTTLPR allele. This polymorphism has been associated with certain comorbid symptoms in some alcoholics.

These data demonstrate that polymorphisms in one gene can have a significant effect on the expression of a second, unlinked, gene. Genetic risk of alcohol misuse may exacerbate the risk of brain damage in susceptible subjects, by modulating the expression of the N-methyl-D-aspartate glutamate receptor and thereby enhancing excitotoxicity in vulnerable brain regions.
Subjects 11 Medical and Health Sciences
1103 Clinical Sciences
1701 Psychology
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
060411 Population, Ecological and Evolutionary Genetics
Keyword Alcohol misuse
Alcohol dependence
Heritability
Strength of craving
Compulsion to drink
Alcohol consumed
Withdrawal symptoms
Genetic control
Neurotransmitter receptor subunit
GluRNMDA
N-methyl-Daspartate glutamate receptor
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Published as Poster no. 27

 
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Created: Thu, 18 Feb 2010, 13:16:53 EST by Maria Campbell on behalf of Faculty of Science