Researchers from the RIKEN Center for Integrative Medical Sciences in Japan and collaborators have used genetic analysis and experiments to discover that the subjective responses of Japanese people to alcohol can be divided into three clear clusters. This research, published in Neuropsychopharmacology, could help identify people at risk for alcohol-related disorders.
It is well known that East Asian populations, including Japanese, have certain genetic variations that influence their response to alcohol. These involve two major genes that affect how we metabolize it—ADH1B, which is involved in the changing of alcohol into a toxic chemical known as acetaldehyde, the chemical mainly responsibility for the discomfort of a hangover—and ALDH2, which is involved in transforming acetaldehyde into a non-toxic compound, acetate. A large number of Japanese people harbor a gene variation that allows a more rapid transformation of alcohol into acetaldehyde, but in addition, many also have a variation in the ALDH2 gene that makes it more difficult for them to change the acetaldehyde into acetate, and this is responsible for the so-called “Asian flush.”
Though this is known, how these variations affect people’s subjective reactions to alcohol are not well understood. To address this, the group, led by Chikashi Terao at RIKEN IMS, did experiments on a cohort of 429 healthy young people who consumed alcohol, recognizing that this inclusion criterium would naturally exclude a minority of Japanese who have a genetic variation that makes it virtually impossible to consume alcohol. They sequenced the genomes of the participants, and had them undergo an experiment in which they received alcohol intravenously over several hours to maintain a given blood-alcohol level and were asked to fill out reports every 30 minutes describing feelings such as being high, being sleepy, or being uncoordinated, which are typical of drunkenness.
The findings were surprising and instructive. The researchers discovered that the participants could be clustered into three groups—people who quickly felt the effects of the alcohol, those who gradually felt the effects grow over time, and others who were relatively intolerant to the effects. Further, these clusters were associated with certain combinations of variations in several genes, including the two major ones, meaning that genetic testing could give a prediction of the subjective response people would have to alcohol.
According to Keiko Hikino of RIKEN IMS, the first author of the paper, “Although it was previously thought that various combinations of risk alleles in ALDH2 and ADH1B produced a wide range of alcohol sensitivities, we discovered, unexpectedly, that they can be simplified into just three patterns. The current study focused on healthy young adults, but in the future, we aim to extend our research toward identifying risk factors for alcohol dependence.”
According to Terao, “Alcohol is a common part of daily life, but it’s responsible for many deaths, and its effects on health are of interest to many people. Our finding that alcohol response in the Japanese population can be classified into three distinct types should make it easier to identify and intervene with individuals at higher risk of alcohol-related health problems.”