Genetic polymorphisms in post-mortem alcoholics

We investigated the hypothesis that alcoholism risk may be mediated by genes for neurotransmitters (dopamine, serotonin, opioid, GABAA and glutamate) associated with the dopamine reward system, and with genes involved in ethanol metabolism and fibrogenesis (ADH2, ADH3, ALDH2, CYP2E1, COL1A2, and ApoE). DNA was extracted from brain tissue collected at autopsy from pathologically characterised alcoholics and controls. PCR-based studies showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2) Taq1 B (p 0.005) and the GABAA 2 subunit C1412T (p 0.007) genes but not with the glutamate receptor subunit gene NR2B (366C/G), the serotonin transporter gene (5HTTL-PR), the dopamine transporter gene DAT1(SLC6A3), the Mu opioid receptor gene MOR1 (A118G and C1031G), the dopamine D2 receptor gene DRD2 Taq1 A or the GABAA 1(A15G), 6(T1519C) and 2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (p 0.024). The genotype for the most active alcohol dehydrogenase ADH3 was associated with a lower risk of alcoholism (p 0.027) and was less prevalent in alcoholics with DRD2 Taq1 A2/A2 (p 0.007), Taq1 B2/B2 (p 0.038) and GABAA-2 1412C/C (p 0.005) and EAAT2 603G/A (p 0.020) genotypes. Combined genotypes of DRD2 Taq1 A and B, GABAA-2, and EAAT2 G603A polymorphisms suggested a concerted influence of dopamine, GABAA and glutamatergic neurotransmitters in the predisposition to alcoholism.