Evidence for early endothelial dysfunction associated with the ALDH2 rs671 gene variant: a preliminary investigation with young East Asians

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that plays an important role in aldehyde detoxification. A large percentage (30-50%) of East Asian populations carries a single point mutation in the ALDH2 gene (ALDH2*2 variant) that causes a severe reduction or lack of ALDH2 enzyme activity, and leads to disrupted cellular homeostasis due to the accumulation of toxic reactive aldehydes. The ALDH2*2 variant has been associated with several degenerative diseases, with evidence suggesting a link to cardiovascular disease, potentially mediated by endothelial dysfunction. This, however, remains to be confirmed. We aimed to investigate whether the ALDH2*2 variant is associated with impaired endothelial function in young, healthy East Asians. Twenty-two participants were genotyped and divided into non-carriers (ALDH2*1/*1; n=12; 7 females and 5 males. Age=23±3 years; height=167.4±8.7 cm; body mass=60.1±9.0 kg) and carriers (ALDH2*1/*2 and ALDH2*2/*2; n=10; 8 females and 2 males; age=24±5 years; height=162.6±10.1 cm; body mass=62.1±9.7 kg) of the ALDH2*2 allele. Endothelial function was assessed via flow-mediated dilation (FMD) following current guidelines. Carriers displayed lower FMD, either absolute or relative, which was not statistically significant but approached significance (unpaired t-test) (FMD%: non-carriers=10.2±1.9% vs. carriers=8.1±3.1%, p=0.079, effect size: Cohen’s D=0.82; FMDabs: non-carriers=0.32±0.06 mm vs. carriers=0.26±0.09 mm, p=0.082, effect size: Cohen’s D=0.78). To conclude, our data seems to suggest that the ALDH2*2 variant impairs endothelial function even in young and healthy individuals without the presence of other stressor agents. Future studies with larger sample size are necessary to confirm our findings.