Impact of ALDH2 genotypes and alcohol consumption on age at first-ever ischemic stroke: A cohort study in Taiwan

The ALDH2*2 allele, common in East Asians, impairs aldehyde metabolism and leads to acetaldehyde accumulation during alcohol consumption. Whether this variant interacts with alcohol use to influence the age at ischemic stroke onset remains unclear. We evaluated the associations between ALDH2*2 and alcohol consumption with age at stroke onset.

We enrolled 930 patients (598 men and 332 women) with first-ever ischemic stroke. Alcohol consumption was dichotomized as heavy (>45 g/day or >300 g/week of ethanol) versus nonheavy (abstinent or ≤45 g/day and ≤300 g/week). Because heavy drinking was rare in women, primary analyses focused on men. Participants were grouped by the ALDH2 genotype (*1/*1 vs. *1/*2 or *2/*2) and drinking category. Clinical variables were compared using analysis of variance and chi-squared tests. Multivariable linear regression, adjusted for smoking, assessed associations with age at stroke onset.

Among men, mean age at stroke onset differed significantly across genotype-drinking groups (p < 0.001). ALDH2*2 carriers with heavy drinking had the earliest onset (56.1 ± 9.6 years), whereas ALDH2*2 carriers with nonheavy drinking had the latest onset (63.6 ± 12.3 years). Relative to *1/*1 with nonheavy drinking, ALDH2*2 carriers with nonheavy drinking had later onset (β = 2.67 years, p = 0.023), while those with heavy drinking had earlier onset (β = -4.61 years, p = 0.048). In the overall cohort, male sex, smoking, and heavy drinking were independently associated with younger onset (β = -3.20, -2.57, and - 3.40 years; p = 0.001, 0.006, and 0.002, respectively).

In East Asian men, heavy alcohol consumption among ALDH2*2 carriers is associated with earlier ischemic stroke onset, suggesting a gene-environment interaction. These findings support genotype-informed lifestyle counseling for stroke prevention.