Genetic Variants Can Alter Risk of Developing Alcohol Dependence
ADH1B*3, a variant of the alcohol dehydrogenase enzyme, is seen almost only among populations with African ancestry, and has been associated with reduced rates of alcohol dependence. The study discovered that greater levels of sedation in African Americans with the variant enzyme may explain their lower rates of alcohol dependence.
McCarthy, corresponding author for the study, explained that in one study of genetic samples from several African groups, the ADH1B*3 variant was found in nearly every group. “Furthermore, prior studies had shown that those with ADH1B*3 had reduced drinking and risk for AD, and this was thought to be due to the different form of ADH enzyme that people with this allele have. The goal of our study was to see if those with ADH1B*3 had different subjective and physiological response to alcohol compared to those who do not. This would be one explanation for why they drank less than others -- they have a different experience from drinking,” he continued.
In the study, 91 African American adults ages 21-26 were given a moderate dose of alcohol (females were given less than males to account for gender differences in alcohol metabolizing). All of the participants had the ADH1B*3 variant, as well as additional polymorphisms that could contribute to the response to alcohol. Prior to drinking alcohol and 2.5 hours following alcohol consumption, the researchers collected information on breath-alcohol concentrations, self-reports on sedation and stimulation, and pulse rates.
The results showed that ADH1B*3 was associated with higher levels of sedation, and a sharper increase in pulse immediately after drinking alcohol. McCarthy explained that this shows that people with this variant experience alcohol differently in that they become more sedated, particularly when their breath-alcohol concentrations were high. He added that this could explain why people with this variant have reduced rates of alcohol dependence: when alcohol makes you tired, you’re less likely to want to drink.
“It is important for genetic research to go beyond demonstrating that a gene is related to a drinking disorder and instead demonstrating the steps by which the gene can exert its influence on that disorder,” McCarthy said.
Lara Ray, assistant professor in the department of psychology and faculty member in the Brain Research Institute at UCLA, added that there has been a lack of focus on minority populations such as African Americans and alcohol dependence. "In the pharmacogenomics era, failure to account for genetic differences in various ethnic groups may perpetuate or even expand health disparities. In this study, the authors do a very nice job of addressing unique risk and protective genetic factors for alcoholism in African Americans,” she said.
McCarthy added that he thinks the research on these gene variants has important implications for understanding why individuals drink and how researchers and healthcare professionals can help people with alcohol dependence.
"The treatment of AD by Antabuse™ (disulfiram) actually mimics what happens in people with ALDH2*2 variants, blocking the breakdown of acetaldehyde,” McCarthy said. “It may be that eventually we can do something similar to reduce heavy alcohol use or other consequences of use by increasing the speed at which alcohol is broken down. There is also extensive research on alcohol-related birth defects and cancers, the risk for which can be affected by these genetic variants. For example, people with ADH1B*3 who still drink might be at increased risk for cancers that result from acetaldehyde."
Ray added that it’s important for people to know that there are multiple genetic and environmental factors that play a role in alcohol dependence, and that it is a multifaceted disorder. "This study provides evidence of genetic influences on one pathway to alcoholism; other pathways may lead to the same outcome as evidenced by the heterogeneity of alcoholism,” she concluded.
Source: Science Daily, Genetic Differences That Make You Sleepy When You Drink Can Also Protect Against Alcohol Dependence, May 4, 2010.