<i>ALDH2</i> rs671 variant allele is associated with higher energy intake in middle-aged and elderly Japanese who routinely consume alcohol

Abstract

Background According to recent reports, individuals with reduced aldehyde dehydrogenase activity may require more energy for the detoxification of aldehydes. Aldehyde dehydrogenase 2 (ALDH2), an ALDH isozyme, is responsible for detoxifying acetaldehyde, an intermediate metabolite of ethanol. Because the variant allele of the rs671 polymorphism of ALDH2 results in a substantial reduction in enzymatic activity, carriers of this variant allele may have a higher energy demand when consuming alcohol than non-carriers. However, no studies have evaluated this phenomenon to date. Method To test the hypothesis, we statistically examined the interactive effects between the rs671 and ethanol consumption on energy intake using cross-sectional data from a population-based cohort study, the Japan Multi-Institutional Collaborative Cohort Study, which was conducted in Saga city between 2005–2007 (N = 12,068). Results General linear regression models adjusted for age, sex, ethanol consumption, current smoking status, years of education, dietary restriction, medical history, and physical activity level revealed that energy intake was higher in variant allele carriers than in non-carriers among individuals with alcohol drinking habits, whereas no such correlation was observed among those without drinking habits (≤2 g ethanol/day) ( p = 0.03 for interaction between rs671 and ethanol consumption). Energy intake excluding energy from alcoholic beverages, carbohydrate intake, protein intake, and fat intake, showed similar tendencies ( p for interaction = 0.01, 0.01, 0.04, and 0.07, respectively). Conclusions These findings support the hypothesis that increased energy intake is required for the detoxification of aldehydes in individuals with low ALDH activity. This epidemiological evidence provides a possible scientific basis for understanding aldehyde detoxification mechanisms and suggests a novel phenotype of the ALDH2 rs671 polymorphism. Supplementary information The online version contains supplementary material available at https://doi.org/10.1265/ehpm.22-00276 .

Asian flush is a potential protective factor against COVID-19: a web-based retrospective survey in Japan

“…The study assumes that flushing predicts rs671 based on previous studies showing its high accuracy, 88–94% [ 28 – 30 ], and an overwhelming association between flushing and rs671 among other gene polymorphisms [ 42 ]. Based on the distribution of rs671 and the frequency of flushers in previous studies in Japan, the rate of flushers was expected to be 46%–51% [ 39 , 43 , 44 ]; however, the proportion in the current study was as high as 55%. We speculate that this was because of false positives, especially in elderly individuals, for the following reason.…”

“…Based on the result of the current study, the effect of rs671 is expected to be greater but not robust enough to be found in GWAS, where adjustment for covariates is limited. Based on previous study findings, rs671 is expected to influence several COVID-19-related traits, such as food preference and underlying metabolic conditions and diseases [ 39 – 41 ], resulting in the inclusion of various noises.…”

The ALDH2 gene rs671 polymorphism is associated with cardiometabolic risk factors in East Asian population: an updated meta-analysis

“…In addition, other literature also discussed the mechanisms between ALDH2 and cardiometabolic risk factors. Previous studies on ALDH2 rs671 polymorphism and T2DM had provided controversial results ( 25 , 35 , 38 , 40 , 57 , 63 , 67 ). This may be due to the sample size of most ALDH2 studies being relatively small (28 included studies of our study had participants less than, 1000), and ALDH2 was interfered with other confounding factors.…”