Alcohol inhibits glutamate transmission and genetic variations in glutamate receptors would have effects on alcohol problems.
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Genetic Variation of the Gene for the NR2A Subunit of the Glutamate NMDA Receptor is Associated with Alcohol Dependence, Earlier Age of Onset, Positive Family History and Maximal Drinking in Adults and Risky Drinking Patterns in 15 y.o. Adolescents
In individuals of German descent, 204 single nucleotide polymorphisms (SNPs) covering 10 glutamatergic genes were evaluated in 1337 adults with alcohol dependence and 1555 controls and 144 adolescent–parent trios. Adults with both C/C genotype of the rs 2072450 and deletion/deletion genotype of the rs 9924016 SNPs were at risk (compared to A/C and deletion/insertion that were protective) and the transmission of the rs 2072450 C allele was the risk allele in adolescents. Alcohol regulates NR2A expression in brain, and NR2A subunits are among the most sensitive NMDA-receptor subunits to the inhibitory effects of alcohol. NR2A knockout mice have no conditioned place preference to alcohol, which suggests that the NR2A polymorphism could result in a reduced response to alcohol that could lead to the development of alcohol dependence.(Constructed from data in Schumann, G. et al. Arch Gen Psychiatry, 65: 826, 2010) ©2010 NBEP
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