Associations of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Polymorphism With Cognitive Impairment Among the Oldest-Old in China.

Xurui Jin,Chenkai Wu,Yi Zeng,Tingxi Long,Huashuai Chen,Lijing Yan,Xian Zhang

doi:10.3389/fnagi.2021.710966

Abstract

Recent literature suggested that ALDH2 mutation is associated with alcohol metabolism, and ethanol intake might jointly increase the risk of Alzheimer’s disease (AD) in mice. However, it is unclear whether this synergistic effect exists among humans. We examined the associations of four single nucleotide polymorphisms (SNPs) on aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) genes (i.e., ALDH2 rs671, ADH1B rs1229984, ADH1B rs1042026, and ADH1C rs1693482) and cognitive impairment among the oldest-old. We also investigated whether this association was modified by ethanol intake from alcohol consumption. Data were from the Chinese Longitudinal Healthy Longevity Survey genetic sub-study, including 1,949 participants aged over 90 years. Participants with a Mini-Mental State Examination (MMSE) score of < 18 were considered cognitively impaired. Alcohol consumption was categorized as heavy, moderate, or never drinkers. With the dominant model, carrying A allele on rs671, C allele on rs1229984, and T allele on rs1042026 was associated with 33% (95% confidence interval [CI]: 5%, 69%), 33% (95% CI: 2%, 75%), and 29% (95% CI: 3%, 62%) higher odds of cognitive impairment in the multivariable-adjusted logistic model, respectively. We did not observe a significant interaction between those SNPs and alcohol consumption. Among the oldest-old, carrying ALDH2 rs671 mutation was associated with higher odds of cognitive impairment independent of alcohol consumption.

Highlights

Aging is a major contributor to cognitive decline and dementia across the world, and it is becoming a major public health concern
Some other genetic studies have found that the negative impact of genetic factors may be cumulative by age, such as apolipoprotein E (APOE) gene on cognitive function, and there is a fewer study of Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes among the oldestold population
Using data from nearly 2,000 Chinese adults aged over 90 years, we found that the single nucleotide polymorphisms (SNPs) on ADH and ALDH2 genes were associated with higher odds of cognitive impairment

Summary

Introduction

Aging is a major contributor to cognitive decline and dementia across the world, and it is becoming a major public health concern. Associations of ALDH With Cognitive Function association studies (GWAS) Those candidate genes include apolipoprotein E (APOE), catechol-O-methyltransferase (COMT) (Komulainen et al, 2008), brain-derived neurotrophic factor (BDNF) (Bray et al, 2005), and dystrobrevin-binding protein 1 (DTNBP1) (Wray et al, 2008), with the APOE ε4 allele being by far the strongest genetic risk factor and accounts for about 5% of the variance in lifetime cognitive change and 4% of the variance in AD. In addition to those genetic factors, some recent works have indicated the key role of some alcohol metabolism-related genes as enzymes involved in the detoxification of the ethanol metabolism in the pathology of AD. Some other genetic studies have found that the negative impact of genetic factors may be cumulative by age, such as APOE gene on cognitive function, and there is a fewer study of ADH and ALDH genes among the oldestold population

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