ALDH2 rs671 and MTHFR rs1801133 polymorphisms are risk factors for arteriosclerosis in multiple arteries

Abstract

Background Arteriosclerosis in multiple arteries has long been associated with heightened cardiovascular risk. Acetaldehyde dehydrogenase 2 (ALDH2) and methylenetetrahydrofolate reductase (MTHFR) play an important role in the pathogenesis of arteriosclerosis by participating in the oxidation and reduction reactions in vascular endothelial cells. The purpose was to investigate the relationship of ALDH2 and MTHFR gene polymorphisms with arteriosclerosis in multiple arteries. Methods 410 patients with arteriosclerosis in single artery and 472 patients with arteriosclerosis in multiple arteries were included. The relationship between ALDH2 rs671 and MTHFR rs1801133 polymorphisms and arteriosclerosis in single artery and arteriosclerosis in multiple arteries was analyzed. Results The proportion of ALDH2 rs671 A allele (35.6% vs. 30.9%, P = 0.038) and MTHFR rs1801133 T allele (32.6% vs. 27.1%, P = 0.012) in patients with arteriosclerosis in multiple arteries was significantly higher than that in arteriosclerosis in single artery, respectively. The proportion of history of alcohol consumption in patients with ALDH2 rs671 G/G genotype was higher than those in ALDH2 rs671 G/A genotype and A/A genotype (P < 0.001). The results of logistic regression analysis indicated that ALDH2 rs671 A/A genotype (A/A vs. G/G: OR 1.996, 95% CI: 1.258–3.166, P = 0.003) and MTHFR rs1801133 T/T genotype (T/T vs. C/C: OR 1.943, 95% CI: 1.179–3.203, P = 0.009) may be independent risk factors for arteriosclerosis in multiple arteries (adjusted for age, sex, smoking, drinking, hypertension, and diabetes). Conclusions ALDH2 rs671 A/A and MTHFR rs1801133 T/T genotypes may be independent risk factors for arteriosclerosis in multiple arteries.

Impact of common ALDH2 inactivating mutation and alcohol consumption on Alzheimer’s disease

“…A role of ALDH2 in BBB integrity has also been suggested. ALDH2 is involved in oxidative and reductive reactions in vascular endothelial cells ( Nannelli et al, 2020 ) and reduced ALDH2 activity is associated with the acquisition of an early aging phenotype of endothelial cells ( Nannelli et al, 2018 ), atherosclerosis ( Cai et al, 2023 ), and coronary artery disease ( Xu et al, 2011 ; Yasue et al, 2019 ). Reduced ALDH2 activity increases 4-HNE-medicated reduction of anti-angiogenesis ( Roy and Palaniyandi, 2020 ) and migration ( Roy et al, 2020 ) in mouse coronary endothelial cells and is involved in 4-HNE-induced endothelial dysfunction and mitochondrial dysfunction in human umbilical vein endothelial cells ( Nannelli et al, 2018 ; Figure 4B ).…”