Evidence for early endothelial dysfunction associated with the ALDH2 rs671 gene variant: A preliminary investigation...

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that plays an important role in aldehyde detoxification. A large percentage (30-50%) of the East Asian population carry 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; FMD_abs: non-carriers = 0.32 ± 0.06 mm vs. carriers = 0.26 ± 0.09 mm, P = 0.082, effect size: Cohen's d = 0.78). In conclusion, our data seem 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.