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Food Types, Dietary Supplements, and Roles
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
The balance between the various ADH and ALDH isoforms regulates the concentration of acetaldehyde, which is important as a key risk factor for the development of alcoholism (49–50). Acetaldehyde dehydrogenase 2 (ALDH2) is the key enzyme responsible for metabolism of the alcohol metabolite acetaldehyde in the liver (49). Certain individuals, usually of Asian origin (China, Japan, Korea, Vietnam), have an inactive mitochondrial ALDH2 because of a genetic ALDH deficiency. Of note, approximately 8% of the world’s population, and approximately 30–40% of the population in East Asia, carry an inactive ALDH2 gene (49). Thus, when these individuals consume ethanol, blood levels of acetaldehyde are 5-to 20-fold higher than those found in individuals with the active ALDH allele. Individuals with the inactive ALDH show marked vasodilator (facial flushing or red face), nausea, headaches, and palpitation when consuming alcohol (50). Acetaldehyde is poorly eliminated by these individuals and as a consequence, little alcohol is consumed. ALDH2 deficient individuals are at lower risk for alcoholism. In contrast, they may have possibly increased risk for liver damage and esophageal cancer if alcohol continues to be consumed due to the accumulation of acetaldehyde in these organs (49–51).
Genetic Studies of PTSD and Substance Use Disorders
Published in Anka A. Vujanovic, Sudie E. Back, Posttraumatic Stress and Substance Use Disorders, 2019
Christina M. Sheerin, Leslie A. Brick, Nicole R. Nugent, Ana B. Amstadter
Most successful findings have provided support for the role of alcohol-metabolizing enzyme (ADH and ALDH) gene clusters in relation to alcohol dependence. Frank and colleagues (2012) identified a significant marker located between the ADH1B and ADH1C genes in a sample of 3,501, and Park et al. (2013) identified two SNPs within ADH7 and a missense SNP in ALDH2 in a smaller sample of 396. Two SNPs in ALDH2 were found to be associated with alcohol dependence among a sample of 374 males (Quillen et al., 2014). Additionally, Gelernter et al. (2014) conducted a GWAS using a large discovery sample (N = 2,379 European Americans and N = 3,318 African Americans) and replication with independent samples (totaling N = 7,152), identifying several genome-wide significant associations using alcohol dependence symptom count at the ADH locus on chromosome 4, PDLIM5, and a novel SNP on chromosome 2 between MTIF2 and CCDC88A present across different samples.
Diet and Cancer Prevention
Published in James M. Rippe, Lifestyle Medicine, 2019
Polymorphisms in ethanol- and acetaldehyde-metabolizing enzymes, especially ADH and ALDH, have been closely associated with ethnic and individual differences in susceptibility to alcohol-related cancers. For example, many individuals of Chinese, Korean, and Japanese descent carry a version of the gene for ADH that codes for a “superactive” form of the enzyme. As a result, they have a quicker conversion of ethanol to acetaldehyde and a higher risk of pancreatic cancer.71 In addition, a genetic variant in ALDH2 that codes for a defective form of the enzyme with no detectable activity causes acetaldehyde accumulation after alcohol drinking; individuals experience facial flushing, tachycardia, nausea, and hypotension.72 This variant is prevalent in Asians, with a frequency of up to 40%, whereas it does not exceed 5% in European and African populations.73 Prospective studies in cancer-free alcoholics have shown that the hazard ratio for future aerodigestive tract cancers in individuals with the inactive protein is approximately 12 times higher than in individuals with the active protein.74 A true understanding of the effect of dietary alcohol may be clouded because of the compounds found in alcoholic beverages including flavonoids, such as resveratrol, which can potentially suppress tumorigenesis.
Hypermethylation of the OPRM1 and ALDH2 promoter regions in Chinese Han males with alcohol use disorder in Yunnan Province
Published in The American Journal of Drug and Alcohol Abuse, 2021
Linlin Liu, Xiaopei Yang, Fei Zhao, Changqing Gao, Ning Zhang, Jianjun Bao, Kuan Li, Xulan Zhang, Xiaoxiao Lu, Ye Ruan, Shurong Zhong
The ALDH2 gene encodes aldehyde dehydrogenase 2, which is the key enzyme in the metabolism of ethanol-derived acetaldehyde in hepatocytes and plays a major role in the kinetics of alcohol clearance. A genome-wide association study (GWAS) found that rs671 in the ALDH2 gene was significantly associated with AUD and its two related phenotypes (blush response and 24-hour maximum alcohol consumption) in the Chinese population (29). Studies showed that rs671 can significantly affect drinking behavior (30,31). The rs671 variant genotype (G > A) is a protective factor of drinking behavior, and individuals with the rs671 variant genotype are less likely to drink (32). Epigenetic studies on AUD have shown that the ALDH2 promoter region is hypermethylated in patients with AUD and that the methylation level correlated significantly with the rs886205 genotype in the disease group (33,34). Interestingly, in the disease group, the methylation level continued to decline to the normal level within 1–14 days of withdrawal treatment (34). Overall, the findings suggest that ALDH2 gene polymorphisms and epigenetics are closely related to AUD in different populations.
College students’ use of strategies to hide facial flushing: A target for alcohol education
Published in Journal of American College Health, 2020
Karen G. Chartier, E. Clare Tiarsmith, Taryn O'Shea, Kenneth S. Kendler, Danielle M. Dick
The alcohol flushing response is an adverse reaction to the metabolism of ethanol,1 which occurs when deficient enzymes for metabolizing ethanol result in a buildup of acetaldehyde in the body.2 Alcohol-related flushing has a genetic basis. Two genetic markers associated with flushing are ADH1B*2 and ALDH2*2. They have different mechanisms affecting flushing; ADH1B*2 initiates a faster metabolism of ethanol to acetaldehyde whereas ALDH2*2 has a slower metabolism of acetaldehyde to acetate. The frequency of these genetic markers varies across populations groups. ADH1B*2 is found in 80% or more of northeast Asians (Chinese, Japanese, and Koreans) and about 10% of individuals of European ancestry.1 The ALDH2*2 variant is found almost exclusively in people of northeast Asian descent with the prevalence varying across specific Asian groups.1
Molecular mechanisms of ethanol biotransformation: enzymes of oxidative and nonoxidative metabolic pathways in human
Published in Xenobiotica, 2020
Grażyna Kubiak-Tomaszewska, Piotr Tomaszewski, Jan Pachecka, Marta Struga, Wioletta Olejarz, Magdalena Mielczarek-Puta, Grażyna Nowicka
Studies have proven the polymorphism of the ALDH2 gene. The ALDH2*1 allele encodes subunits which guarantee the formation of an active form of ALDH2 isoenzyme after tetramerisation. The ALDH2*2 alternative allele results from a point mutation consisting of a G → A transition codes of the defective subunits having lysine instead of glutamate at position 487. Including at least one such subunit in the structure of the tetramer leads to the creation of a form of isoenzyme which is about 100 times less active and thus called, more simply, inactive. Thus, ALDH2*2 is the dominant allele. In ALDH2*2 homozygotes only the inactive form of ALDH2 isoenzyme is present. This situation is encountered in more than 50% of the Oriental population. Only about 6.25% of ALDH2 active forms are found in heterozygotes because of low probability of not building the subunit which is the product of ALDH2*2 allele expression. The prevalence of ALDH2*2 allele in the Oriental population determines their increased susceptibility to the toxic effects of acetaldehyde (ExPasy, 2020; Li et al., 2001; WolFF, 1972; Yoshida et al., 1983, 1984). In the absence of ALDH2 activity, the cytoplasmic isoenzyme ALDH1A1, which under physiological conditions is mainly involved in retinal oxidation, gains decisive importance in acetaldehyde metabolism. The competition of ethanol leads to an impairment of retinal metabolism, underlying growth and cell differentiation disorders (Dockham et al., 1992; Maly et al., 1999; Wang et al., 1998).