Background Human twin studies have shown that certain responses to alcohol, including subjective perceptions, are genetically influenced. Previous studies have provided evidence that a low level of response to alcohol predicts future alcohol use disorders in humans. Recent genetic studies suggest an association between alcohol dependence and genetic variation in the γ-aminobutyric acid A (GABAA) receptor α2 subunit gene (GABRA2). Based on a haplotypic association of alcohol dependence with GABRA2, we investigated whether GABRA2 alleles are associated with the subjective responses to clamped alcohol concentration. Methods One hundred and ten healthy social drinkers (53 men) underwent the alcohol clamp. Fifteen minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 50 ± 5 mg/dl for 165 minutes. Subjective physiologic responses to alcohol and stimulant and sedative effects of alcohol were measured repeatedly during the alcohol clamp. Because aldehyde dehydrogenase 2 (ALDH2) has been shown to have a great impact on the subjective responses to alcohol, we divided subjects by ALDH2 genotype for further analyses. To examine the role of genetic variation in GABRA2, 7 single nucleotide polymorphisms (SNPs) that were informative in association studies were included as factors in the analysis. Results Among these 7 SNPs, 3 SNPs (rs279869, rs279858, and rs279837) located in the middle of the GABRA2 gene showed significant associations with subjective effects of alcohol. Subjects with 1 or 2 copies of the more common allele showed greater subjective responses to alcohol than did individuals homozygous for the alcohol dependence–associated allele regardless of ALDH2 genotype. Conclusions These findings confirm and extend the observation that the GABRA2 alleles affect the subjective responses to alcohol, and suggest that the genetic variations in GABRA2 might play a role in the risk of alcohol use disorders by moderating the subjective effects of alcohol.

AimsThe purpose of this paper is to outline alcohol availability, alcohol consumption and related harm, alcohol control policy and prevention programmes in Japan, few of which have been discussed in either the Japanese or English literature. Methods Data were collected primarily from the following two sources: statistics and survey results issued by the national government, including surveys funded by the government; and papers published since 2000, identified by searching the MEDLINE and Igaku-Chuo-Zasshi databases. These data were assessed regarding their quality and summarized. Some data presented here were produced specifically for this review. Results Although per capita alcohol consumption has tended to decline for more than 10 years, it has remained at a high level. Diversification of the drinking population has progressed rapidly, specifically in women, among whom alcohol consumption has increased sharply. Cross-sectional data suggest that alcohol consumption is associated with serious health and social consequences. Existing longitudinal data suggest that alcohol-related problems, especially health problems, have increased steadily over the past several decades, with few exceptions, including alcohol-related fatal road traffic accidents. Alcohol policy and prevention programmes have not developed to a level that can control these problems adequately. Specifically, the high availability of alcoholic beverages, including the lack of restrictions on sales and advertising and decreasing prices, are noted. Conclusions This review provides basic information regarding alcohol availability and alcohol consumption and related harm that may facilitate the improvement of existing alcohol control measures in Japan and encourage the development of new alcohol control measures. This research revealed the scarcity of longitudinal data regarding alcohol consumption and its consequences, and the lack of several important variables, such as disability adjusted life years, for improving our understanding of the comprehensive status of alcohol in Japan.

Intense neuronal cell death occurs transiently in WE, and the mechanism differs from that in AD. Neuronal damage is generally unaccompanied in WD. These results suggest that CSF total tau is a useful biological marker for WE.