國家衛生研究院 NHRI:Item 3990099045/13267
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    題名: Association study of alcohol dehydrogenase and aldehyde dehydrogenase polymorphism with Alzheimer disease in the Taiwanese population
    作者: Wu, YY;Lee, YS;Liu, YL;Hsu, WC;Ho, WM;Huang, YH;Tsai, SJ;Kuo, PH;Chen, YC
    貢獻者: Center for Neuropsychiatric Research
    摘要: 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 ADH/ALDH single-nucleotide polymorphisms (SNPs), ADH1C rs2241894, ADH1B rs1229984, ALDH1B1 rs2073478, ALDH2 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 ADH/ALDH SNPs. Reconstructed ALDH2 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 ADH1C rs2241894 TT genotype was negatively associated with AD in a recessive genetic model (OR = 0.25, 95% CI 0.09-0.75, p < 0.0001) in women. A strong linkage disequilibrium was observed among the four examined SNPs of ALDH2. 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 (p = 0.04). This interaction effect was attributable to the association between AD and plasma ADH1C level (beta estimate = 366, 95% CI 92.7 similar to 639.4, p = 0.009). The genetic distribution of ADH1C 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.
    日期: 2021-01-22
    關聯: Frontiers in Neuroscience. 2021 Jan 22;15:Article number 625885.
    Link to: http://dx.doi.org/10.3389/fnins.2021.625885
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1662-453X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000614741400001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85100523576
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