An East Asian-specific genetic variant, the rs671 variant in the aldehyde dehydrogenase 2 (ALDH2) gene, tends to receive attention due to its disadvantages, including alcohol-induced cancer [1] and cognitive dysfunction [2]. However, emerging evidence suggests that this variant also confers advantages, such as increased resistance to infectious diseases [3] and decreased risk of addiction [4].

We read the recent report by Chen et al. [5] with great interest. The authors investigated the effect of the rs671 variant on the risk of ruptured intracranial aneurysm (RIA), a life-threatening condition with a high fatality rate. Epidemiological evidence has shown a higher incidence of RIA in the Japanese population than in Western populations [6], prompting speculation that the East Asian-specific rs671 variant may be a risk factor for RIA. However, to the best of our knowledge, this study is the first to report that the rs671 variant may protect against RIA.

In the multivariate logistic regression analysis conducted by the authors, the rs671 variant group had a decreased odds ratio (OR) for RIA, even after adjusting for key contributing variables, including sex, age, hypertension, smoking, and alcohol consumption (OR: 0.49; 95% confidence interval 0.27-0.88). This suggests that the association is independent of traditional risk factors. However, we would like to highlight a point of confusion in the discussion section. The second sentence in the discussion challenges this interpretation, potentially confusing readers. The authors state that “Alcohol consumption significantly influenced the relationship between ALDH2 polymorphisms and the risk of RIA, especially among individuals with the ALDH2*1/*1 genotype, whereas no significant associations were found with other vascular risk factors”; however, this conclusion is not supported by their findings.

Since carriers of the rs671 variant have a low acetaldehyde detoxification ability, acetaldehyde accumulates in their bodies after ethanol ingestion and exhibits a strong vasodilatory effect [7,8]. This suggests that the effect of alcohol consumption on RIA may interact with the rs671 variant. Additionally, the authors failed to calculate the OR for the heavy drinking stratum in Table 5, presumably due to the limited number of heavy drinkers among the rs671 variant carriers.

To address these issues, we recommend incorporating additional statistical models that include an interaction term between rs671 and alcohol consumption. Stratification by the presence or absence of the rs671 variant to examine the effect of alcohol would also help clarify this association. These models could provide more insights into how alcohol consumption affects RIA risk differently depending on the rs671 genotype.

We commend the authors for this important contribution and hope that further analyses will clarify the complex relationship between genetics and lifestyle factors in RIA risk.