We have tested for effects of alcohol dehydrogenase v\DH) genotypes on self-reported alcohol consumption and symptoms of alcohol dependence, recorded on three occasions up to 15 years apart, in 377 male and female subjects of European descent. ADH2 genotype had significant effects on both consumption and dependence in the men, but not in the women. The effects of ADH3 genotype were considerably less than those of ADH2, but significant results could be demonstrated when the combined genotypes were considered. The direction of the effects on alcohol consumption and dependence risk were consistent with reports on Asian subjects, and with the in vitro properties of ADH isoenzymes. As with previous studies on the relationship between ADH type and alcohol use, population stratification cannot be excluded as a contributing factor in these results.Key Words: Alcohol Dehydrogenase, Alcoholism, Association, Female, Male.ULTIPLE REPORTS'-9 indicate that alcohol dehy-M drogenase (ADH)2 and ADH3 genotypes influence the risk of alcohol dependence among Japanese or Chinese subjects, independent of aldehyde dehydrogenase (ALDH) g e n~t y p e . ' ,~,~.~ Meta-analysis of these reports" shows that the relative risk for alcohol dependence increases -3-fold for each copy of ADH2*1 and a similar amount for each copy ofADH3*2-but, on present evidence, in Asians only.The alleles associated with lower risk (ADH2*2 and ADH3*1) code for proteins with greater in vitro enzymatic activity." This is consistent with the hypothesis2 that faster conversion of ethanol to acetaldehyde deters subjects from alcohol consumption, although it has not yet been demonstrated that acetaldehyde concentrations are higher nor that ethanol metabolism is faster in vivo in subjects with these forms of ADH. From the in vitro data, the effect of ADH2 type should be greater than that ofADH3 so that the order of rates of alcohol metabolism would beADH2*22 > 12 > 11 and within eachADH2groupADH3*11 > 12 > 22.On this hypothesis, the risk of alcohol dependence, or the quantity of alcohol used and the number of problems encountered, would trend in the opposite direction. However, studies on ADH2 genotypes in other, nonAsian populations have produced negative re~ults.'~-'~ This might be because of the low prevalence of ADH2*2 in non-Asian groups, or because of some factor that modifies the effects of genotype and that differs between populations. ForADH3, there are indications" that the significant effects found in Asian populations do not extend to European ones. Therefore, it is desirable to assess the effects of ADH genotype in diverse non-Asian groups in order to determine whether these effects are universal.We have data on lifetime prevalence of alcohol dependence, together with measures of alcohol consumption and alcohol-related problems, in a group of subjects of European descent studied on multiple occasions over the past 19 years. We have therefore tested for association between ADH2 or ADH3 genotype and these alcohol-related variables, and the expected trend acr...

To determine the influence of concurrent human immunodeficiency virus (HIV) infection on chronic hepatitis B virus (HBV) infection, 150 male homosexual chronic hepatitis B surface antigen (HBsAg) carriers were studied. Of these, 82 subjects (55%) tested positive for antibodies to HIV. They were more likely to express hepatitis B "e" antigen (HBeAg) (P less than .001) and HBV-DNA (P less than .0005) in serum than were HIV-seronegative individuals. However, the degree of immune suppression did not influence HBeAg-HBV-DNA expression. In HBeAg-seropositive subjects, concurrent HIV infection was associated with lower serum alanine transferase levels (P less than .001). This effect increased with the degree of immune suppression as determined by CD4+ lymphocyte counts. Conversely, in patients negative for HBeAg, there was a weak trend towards higher alanine transferase levels with concurrent HIV. This study suggests that chronic hepatitis B may be less severe when accompanied by HIV infection; however, greater viral replication may make it more contagious and resistant to antiviral therapy. These data support an immune-mediated pathogenesis for hepatitis B and have implications for its control.