ALDH2 and ADH1B interactions in retrospective reports of low-dose reactions and initial sensitivity to alcohol in Asian American college students.

BACKGROUND: A mechanistic model has been proposed for how alcohol-metabolizing gene variants protect individuals from the development of alcohol use disorders, with heightened sensitivity to alcohol being an early step (endophenotype) in this model. This study was designed to determine whether possession of 2 alcohol-metabolizing genes variations, the aldehyde dehydrogenase ALDH2*2 allele and the alcohol dehydrogenase ADH1B*2 allele, was associated with self-reported sensitivity to alcohol at low doses and at initial use. METHODS: Asian-American college students (N=784) of Chinese and Korean descent were genotyped at the ALDH2 and ADH1B loci and assessed for lifetime alcohol symptoms following 1 or 2 drinks and level of response to alcohol during the first 5 lifetime drinking episodes. RESULTS: Participants who had an ALDH2*2 allele were more likely to report experiencing all 6 low-dose symptoms and having heightened initial response to alcohol. An interaction was found between ALDH2*2 and ADH1B*2, with ADH1B*2 being associated with heightened self-reported sensitivity to alcohol only in individuals who also possessed 1 ALDH2*2 allele. CONCLUSIONS: These findings suggest the effects of ADH1B*2 may be felt more strongly in Asians who already have some heightened sensitivity to alcohol from possessing 1 ALDH2*2 allele, but who are not too sensitized to alcohol from possessing 2 ALDH2*2 alleles. These results offer additional insight into the discrepant findings that have been reported in the literature for the role of ADH1B*2 in response to alcohol and the development of alcohol-related problems.

ALDH2*2 is associated with a decreased likelihood of alcohol-induced blackouts in Asian American college students.

OBJECTIVE: A recent report found the heritability estimate for alcohol-induced blackouts was 53%. The present study was designed to determine whether possession of two specific genetic variations, an aldehyde dehydrogenase ALDH2*2 allele and an alcohol dehydrogenase ADHIB*2 allele, were associated with lower rates of lifetime blackouts. METHOD: Asian American college students (N=403) of Chinese and Korean descent were genotyped at the ALDH2 and ADHIB loci and assessed for lifetime alcohol-induced blackouts and the maximum number of drinks ever consumed in a 24-hour period. RESULTS: Participants who had an ALDH2*2 allele had approximately one third the risk of having a lifetime blackout of participants without this allele. Rates of experiencing a lifetime blackout did not significantly differ by ADHIB*2 status. Possessing an ALDH2*2 allele was associated with decreased risk of lifetime blackouts even after controlling for maximum number of drinks ever consumed in a 24-hour period and ethnicity. CONCLUSIONS: These findings suggest the protective effects of possessing an ALDH2*2 allele include a lowered risk of experiencing alcohol-induced blackouts.

Genetic associations of alcohol dehydrogenase with alcohol use disorders and endophenotypes in white college students.

Associations of alcohol dehydrogenase (ADH) gene polymorphisms (ADH1B*2 and ADH1C*1) with a lifetime alcohol use disorder (AUD) were examined in White college students. Alcohol-related endophenotypes likely to be influenced by elevations in acetaldehyde were also assessed. Individuals with an ADH1B*2 allele had lower rates of AUDs, consumed a lower maximum number of drinks in a 24-hr period, reported a greater level of response to alcohol, were more likely to have experienced alcohol-induced headaches following 1 or 2 drinks, and reported more severe hangovers than those lacking this allele. These findings are consistent with the hypothesis that enhanced sensitivity to alcohol and lower levels of alcohol use reflect the mechanism by which ADH1B*2 protects against developing an AUD.

Associations of ALDH2 and ADH1B genotypes with response to alcohol in Asian Americans.

OBJECTIVE: Individuals with alcohol dependence are less likely to possess variant alleles of the alcohol-metabolizing genes, aldehyde dehydrogenase (ALDH2*2) and alcohol dehydrogenase (ADH1B*2), than non-alcohol-dependent controls. It is hypothesized that the mechanism through which these alleles protect against alcohol dependence is by causing elevations in acetaldehyde, which in turn cause an increased response to alcohol. Previous research has shown that individuals with ALDH2*2 demonstrate enhanced reactions to alcohol compared with those without this genetic variant, but evidence that ADH1B*2 is associated with a greater alcohol response is mixed. This study was designed to determine whether the ADH1B genotype is associated with more intense reactions to alcohol after controlling for the ALDH2 genotype. METHOD: Participants (N = 101) were Asian American college students. Each was evaluated using objective and subjective measures before and after ingestion of alcohol and placebo beverages. RESULTS: Participants with the ALDH2*1/*2 and ALDH2*2/*2 genotypes were more likely to experience vomiting following ingestion of the alcohol beverage than those with the ALDH2*1/*1 genotype. Participants with the ALDH2*1/*2 genotype also had greater pulse-rate increases, observed flushing ratings, and subjective feelings of intoxication 30 minutes after ingestion of alcohol than participants with the ALDH2*1/*1 genotype, despite equivalent blood alcohol concentration (BAC) measurements. Among participants with the ALDH2*1/*1 genotype, there were no additional effects of the ADH1B genotype on any measures of response to alcohol. Among participants with the ALDH2*1/*2 genotype, those with the ADH1B*2/*2 genotype were more likely to experience alcohol-induced vomiting and to report feeling less "great overall" 30 minutes after ingestion of alcohol than those with the ADH1B*1/*2 genotype. CONCLUSIONS: These findings are consistent with the hypothesis that there is an additional effect of ADH1B*2 on level of response to alcohol, but only among individuals with the ALDH2*1/*2 genotype.

ALDH2 status and conduct disorder mediate the relationship between ethnicity and alcohol dependence in Chinese, Korean, and White American college students.

This study examined aldehyde dehydrogense (ALDH2) gene status, alcohol dehydrogense (ADH2) gene status, conduct disorder, and alcohol dependence in Chinese, Korean, and White American college students. Chinese had a lower rate of alcohol dependence (5%) than Koreans (13%) and Whites (17%). Koreans had a higher rate of conduct disorder (15%) than Whites (9%) and Chinese (6%). The relationship of ethnicity to alcohol dependence was mediated by ALDH2 status and conduct disorder, although Chinese ethnicity remained significant. ADH2 status was not related to alcohol dependence with ALDH2 included, and no interactions were significant. Results suggest that different rates of risk (e.g., conduct disorder) and protective (e.g., ALDH2 status) factors partially account for ethnic differences in rates of alcohol dependence.

Genetic risk for alcoholism relates to level of response to alcohol in Asian-American men and women.

OBJECTIVE: Previous studies have shown that Asians who possess a variant aldehyde dehydrogenase allele (ALDH2*2) have lower rates of alcohol consumption and dependence. Research in Asian men has shown that those with ALDH2*2 have greater responses to alcohol than do those without this genetic variant. The present study was designed to determine whether similar levels of response to alcohol, using objective and subjective measurements, are seen in men and women with different ALDH2 genotypes. METHOD: Participants (N = 30) were 16 men and 14 women, of whom five each were heterozygous for ALDH2*2. They were evaluated in response to alcohol and placebo beverage challenges, dosed according to estimated body water. Objective and subjective responses were measured every 30 minutes from baseline to 150 minutes after ingestion. RESULTS: Men and women with ALDH2*1/*2 had greater pulse-rate increases, greater observed flushing responses and greater subjective feelings of being dizzy, drunk and high compared with ALDH2*1/*1 participants, despite having equivalent breath alcohol concentrations. ALDH2*1/*2 participants also reported being less likely to drive, following this level of intoxication, compared with ALDH2*1/*1 participants. Some gender differences were found in subjective, but not objective, responses to alcohol, with women reporting lower levels of being high, nauseated and uncomfortable and having a lower total subjective rating scale score. CONCLUSIONS: This study suggests that low risk for alcoholism based on possession of an ALDH2*2 allele relates to greater response to alcohol in both men and women.

Binge drinking in Jewish and non-Jewish white college students.

BACKGROUND: In the United States, religious commitment, as measured by service attendance, has an inverse relationship with alcohol consumption, heavy use, and problem use. This association, however, has not been found consistently in Jewish Americans. The present study examined the relationship between religious variables and binge drinking in Jewish and non-Jewish white college students. In addition, the association among genetic, cultural, and religious variables and binge drinking was examined in the Jewish sample alone. METHODS: Participants were 132 Jewish and 147 non-Jewish white college students. All participants completed the Time-Line Follow-Back, had blood drawn for genotyping at the alcohol dehydrogenase locus ADH2, and reported their religious affiliation and the number of religious services attended in the past year. Jewish subjects also completed the Jewish Identity Scale. RESULTS: As hypothesized, more frequent religious service attendance related to lower rates of binge drinking in non-Jews but was not related to binge drinking in Jews. Within the Jewish sample, individuals who were religiously affiliated had approximately one third the risk of binge drinking as those who were secularly affiliated, but identification with Jewish culture was not related to binge drinking. In the total sample, individuals who possessed a variant alcohol dehydrogenase allele ADH2*2 were approximately half as likely to binge drink as those who did not possess this allele. CONCLUSIONS: These results are consistent with previous studies that find an inverse relationship between religious service attendance and heavy alcohol use in Christian but not Jewish college students. Findings within the Jewish sample support theories that suggest religious, not just cultural, Jewish affiliation relates to lower levels of alcohol behavior. More research is needed to identify additional factors, including other religious, cultural, genetic, and biological influences, that protect Jewish Americans from heavy drinking.