Association Study of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Polymorphism With Alzheimer Disease in the Taiwanese Population

• Published in: Frontiers in neuroscience 2021-01, Vol.15, p.625885-625885
• Main Authors: Wu, Yah-Yuan, Lee, Yun-Shien, Liu, Yu-Li, Hsu, Wen-Chuin, Ho, Wei-Min, Huang, Yu-Hua, Tsai, Shih-Jen, Kuo, Po-Hsiu, Chen, Yi-Chun
• Format: Article
• Language: English
• Subjects: ADH1C level; ADH1C rs2241894; Age; Alcohol; Alcohol dehydrogenase; Aldehyde dehydrogenase; Alleles; Alzheimer's disease; Biobanks; Dehydrogenases; Dementia; Dementia disorders; Diabetes mellitus; Disease; Enzymes; Gene polymorphism; Genes; Genomes; Haplotypes; Linkage disequilibrium; Metabolism; Metabolites; Neurodegenerative diseases; Neuroscience; Older people; Oxidative stress; Polymorphism; Population genetics; Single-nucleotide polymorphism
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2021.625885

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are two major alcohol-metabolizing enzymes. Moderate alcohol intake is a protective modified factor in Alzheimer's disease (AD) while heavy alcohol intake and abstinence increased dementia risk. The associations between Alzheimer's disease and alcohol-metabolizing genes are uncertain. This study examined the association of AD with seven single-nucleotide polymorphisms (SNPs), rs2241894, rs1229984, rs2073478, rs886205, rs4767944, rs4648328, and rs671. We enrolled 157 AD and 168 age- and sex-matched control subjects in pilot study to examine the association of AD with SNPs. Reconstructed haplotypes were performed. We measured plasma level of ADH1C and checked the interaction effect of AD-rs2241894 genotype on plasma ADH1C level. In extension study, we further examined 339 AD and 2,504 healthy control from the Taiwan Biobank. In pilot study, we observed that rs2241894 TT genotype was negatively associated with AD in a recessive genetic model (OR = 0.25, 95% CI 0.09-0.75, < 0.0001) in women. A strong linkage disequilibrium was observed among the four examined SNPs of . No haplotype was related to AD. The plasma ADH1C level in AD was higher than that in control. After adjusted by age, sex, hypertension, diabetes mellitus, and alcohol, we found a significant interaction effect of AD-rs2241894 genotype on plasma ADH1C level ( = 0.04). This interaction effect was attributable to the association between AD and plasma ADH1C level (β estimate = 366, 95% CI 92.7∼639.4, = 0.009). The genetic distribution of rs2241894 showed strong ethnic heterogeneity, in which the T allele was the minor allele accounting for 28.5% in our study and 23.6% in East Asians, while it was a major allele in Americans, Europeans, and the global populations. No association was discovered between AD and the five SNPs: rs2241894, rs1229984, rs2073478, rs886205, and rs671 in the extension study. In summary, this study revealed a suggestive association between ADH1C rs2241894 and female AD in the pilot study, but failed to confirm this finding in a population database. Further age-matched and large sample size case-control studies are needed before rs2241894 can be interpreted as a protective genetic factor of AD.