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

Background: Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. Many inflammatory cytokines such as tumor necrosis factor (TNF) are produced rapidly in the brain by experimental or clinical injury. Method: To investigate whether genetic polymorphism of TNF was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the TNF-β genes in 72 male alcoholics. Computed tomography was used to determine the severity of brain atrophy. Results: Digestion with NcoI and MspI after polymerase chain reaction amplification showed that the TNFB 1 allele frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (X 2 = 10.20, p = 0.0034). A multivariate analysis that included age, total alcohol intake, ADH2 genotype, and TNF-β genotype showed that the ADH2 1 /2 1 genotype and TNFB 1 /B 1 genotype are independently associated with alcoholic brain atrophy. These findings suggest that the TNFB 1 allele may be associated with alcoholic brain atrophy.