Association of Restriction Fragment‐Length Polymorphisms in the Alcohol Dehydrogenase 2 Gene with Alcoholic Brain Atrophy

Abstract

Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. To investigate whether genetic polymorphism of alcohol-metabolizing enzymes [including alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the ADH2 and ALDH2 genes in 77 male alcoholics. Computed tomography was used to determine the severity of brain atrophy. Digestion with MaeIII and MboII after polymerase chain reaction amplification showed that the ADH2(1) gene frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (chi 2 = 9.274, p < 0.01), whereas no significant association was observed between brain atrophy and the ALDH2 gene Multivariate analysis (including age, total alcohol intake, liver cirrhosis, and ADH2 genotype) showed that the ADH2(1)/ADH2(1) genotype was associated with alcoholic brain atrophy. These findings suggest that the ADH2(1) allele may be associated with alcoholic brain atrophy.

Chinese Alcoholic Patients With Esophageal Cancer Are Genetically Different From Alcoholics With Acute Pancreatitis and Liver Cirrhosis

“…They also found that the alcoholic patients with more severe brain atrophy had a lower incidence of liver cirrhosis (21). Their data support our conclusions that there are different alcoholic subpopulations that are genetically different and acquire different diseases.…”

“…Two lines of evidence indicate that it is possible patients with different organ-specific complications are genetically different. Firstly, Maezawa et al reported that the allele frequencies of ADH2*1 were different in Japanese alcohol-induced brain atrophy patients and alcohol-induced liver cirrhosis patients (21). Secondly, in one study, we concluded that Chinese patients with alcohol-induced cirrhosis and with alcohol-induced acute pancreatitis were two different subpopulations because the allele frequencies of ADH2*1 were different in two patient groups (22).…”

Polymorphism of Tumor Necrosis Factor‐β and Alcohol Dehydrogenase Genes and Alcoholic Brain Atrophy in Japanese Patients

“…The involvement of polymorphic ADH2 genes in alcoholic cirrhosis, alcoholic pancreatitis, alcoholic brain atrophy, and alcohol-induced hyperuricemia has been reported in previous studies (Chao et al, 1994(Chao et al, , 1997Matsumoto et al, 1996;Yamauchi, 1998;Yamauchi et al, 1995Yamauchi et al, , 1999. We have reported that the ADH2 1 allele is associated with the development of alcoholic brain atrophy (Maezawa et al, 1996).…”

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

“…Studies which demonstrate that alcohol drinking (Tyas et al, 2000) and ALDH2*2 alleles (Kamino et al, 2000) increase the risk for Alzheimer's disease support the role of AcH in this type of brain damage. On the other hand, findings that the ALDH2 polymorphism is not associated and that the ADH2*1 allele is associated with alcoholismassociated Korsakoff syndrome (Matsushita et al, 2000) and brain atrophy (Maezawa et al, 1996) speak against the AcH theory. Thus, the open question remains: Which of the different types of alcoholic brain damage, if any, are associated with AcH?…”