Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver

Chiang, Chien-Ping; Lai, Ching‐Long; Lee, Shiao-Pieng; Hsu, Wan-Lin; Chi, Yu-Chou; Gao, Hong‐Wei; Yao, Chung-Tay; Chau, Gar‐Yang; Yin, Shih‐Jiun

doi:10.1097/fpc.0000000000000205

Cited by 16 publications

(21 citation statements)

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“…Minor allele (A allele) of rs671 results in reduced ALDH2 enzymatic activity. Approximately 30% of people in Asia and 47% of those in Taiwan carrying the rs671 A allele [21][22][23][24] . In the male Japanese population, the ALDH2 rs671 GG genotype is associated with cerebral lacunar infarcts 17 .…”

Section: Discussionmentioning

confidence: 99%

“…The cytogenetic location of ALDH2 is 12q24. In the literature review, approximately 30% people in Asia and 47% in Taiwan were described to carry genetic variants of the A allele in ALDH2 with reduced enzymatic activity [21][22][23] . We selected the ALHD2 rs671 (G > A, missense variant Glu504Lys, exon 12), ALDH2 rs4648328 (C > T, intron variant, intron 3), and ALDH2 rs886205 (G > A, promoter, 5′-untranslated region) based on previous evidence of its association with alcohol dependence 26,31 .…”

Section: Selection Of Snp and Genotypingmentioning

confidence: 99%

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Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Huang

Chang

Lee

et al. 2020

Sci Rep

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Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) encode essential alcoholmetabolizing enzymes. While alcohol use is associated with spontaneously deep intracerebral haemorrhage (SDicH), particularly in males, the activities and genetic variants of ADH and ALDH may affect SDICH development. This case-control study was conducted to identify the interaction of alcohol use and SDICH with five single-nucleotide polymorphisms (SNPs): ADH1B rs1229984, ADH1C rs2241894, ALDH2 rs671, ALDH2 rs886205, and ALDH2 rs4648328. We enrolled 208 patients with SDICH and 244 healthy controls in a Taiwanese population. ALDH2 rs671 was significantly associated with SDicH in the dominant (P < 0.001) and additive models (P = 0.007). ALDH2 rs4648328 was borderline significantly associated with SDICH in the recessive (P = 0.024) or additive models (P = 0.030). In alcohol-using patients, the ALDH2 rs671 GG genotype was associated with SDICH risk compared to the GA+AA genotype (P = 0.010). ADH1B rs1229984, ADH1C rs2241894, and ALDH2 rs886205 did not demonstrate association with SDicH. thus, the ALDH2 rs671 GG genotype is a risk factor for SDICH. Because the genetic distributions of ALDH2 rs671 exhibited strong ethnic heterogeneity, further studies in different populations are needed to validate these findings. Primary intracerebral haemorrhage (ICH), accounting for 22-35% of all cases of stroke in Asian populations 1 , is the most devastating stroke subtype with high rates of death and long-term disability in adults 2,3. Asian populations have higher incidences of primary ICH than Caucasians 2. Sixty to eighty percent of primary ICH cases occur at the non-lobar region, including the basal ganglia, thalamus, brain stem, and cerebellum, and are also known as spontaneously deep intracerebral haemorrhage (SDICH) 4. Numerous factors, such as hypertension and alcohol use, have been proposed to contribute to SDICH development 5,6. Alcohol use was associated with an increased ICH risk 7. Alcohol is primarily metabolized by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) 8. The metabolism of alcohol produces acetaldehyde, acetate, and reactive oxygen species (ROS). Excessively produced acetaldehyde and ROS, which are highly reactive and toxic by-products, are distributed throughout cell membranes and interact with certain proteins, affecting cell function and leading to organs damage. The accumulation of acetaldehyde causes oxidative damage, excessive autophagy, decreased myofilament calcium sensitivity, and impaired endoplasmic reticulum calcium-ATPase function 9. Acetate metabolism involved in lipid biosynthesis in the mitochondria of brain tissues 10. In animal models, toxic aldehydes enlarged the cerebral ischaemia-induced infarct area and increased oxidative stress 11,12. Deceased enzymatic activity of ALDH, a condition which impairs the degradation of acetaldehyde, could be

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Section: Discussionmentioning

confidence: 99%

Section: Selection Of Snp and Genotypingmentioning

confidence: 99%

Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Huang

Chang

Lee

et al. 2020

Sci Rep

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“…Thus, the alcohol consumption per body weight was 33% higher in the female patients than in the male patients. Excessive drinking amplifies the modest effect of the ADH1B*1/*1 genotype on the slow elimination of alcohol [31,32], leading to a much longer exposure to high ethanol concentrations compared with that in ADH1B*2 carriers [32,33]. Furthermore, some ADH1B*1/*1 patients may start to drink again when residual alcohol is still present in their system from their previous drink.…”

Section: Discussionmentioning

confidence: 99%

“…The confounding factors that were added to the models were age, usual alcohol consumption, daily number of cigarettes currently smoked, body mass index (BMI), MCV, and ADH1B and ALDH2 genotypes. We combined the ADH1B*1/*2 genotype carriers and the ADH1B*2/*2 genotype carriers into a group with the ADH1B*2 allele because of the semi-dominant nature of the ADH1B*2 allele [27,28]. P values were adjusted for multiple testing by Bonferroni-Holm’s method where appropriate.…”

Section: Methodsmentioning

confidence: 99%

Endoscopic screening using esophageal iodine staining and genotypes of ADH1B and ALDH2 in Japanese alcohol-dependent women

Yokoyama

Omori

et al. 2019

PLoS ONE

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BackgroundThe presence of large or multiple esophageal distinct iodine-unstained lesions (DIULs) is a strong predictor of field cancerization in the upper aerodigestive tract. Several risk factors for DIULs, including genetic polymorphisms of alcohol and aldehyde dehydrogenases (ADH1B, rs1229984; ALDH2, rs671), have been demonstrated in Japanese alcohol-dependent men. However, few evaluations of alcohol-dependent women have been conducted in this field.MethodsUsing multiple logistic regression models, we investigated the results of screening using esophageal iodine staining and the identification of determinants for esophageal DIULs in 472 Japanese alcohol-dependent women.ResultsDIULs ≥5 mm, multiple DILUs, and both characteristics were observed in 35 (7.4%), 31 (6.6%), and 16 (3.4%) patients, respectively. DIULs ≥5 mm were histologically diagnosed as low-grade intraepithelial neoplasia in 26 patients and superficial squamous cell carcinoma in 9 patients. Although the inactive heterozygous ALDH2*1/*2 genotype was more common (33.3% vs. 11.4%, p = 0.002) in the group with DIULs ≥5 mm than in the group without DIULs ≥5 mm, no significant differences in the results of a questionnaire asking about current and past facial flushing after a glass of beer were seen between the groups with and without DIULs ≥5 mm. When individuals with current or former flushing were assumed to have inactive ALDH2, the sensitivity and specificity of current or former flushing to identify the presence of inactive ALDH2 were 50.0% and 93.5%, respectively; these values were previously reported to be 88% and 92%, respectively, in a Japanese general female population. The low sensitivity in the present study suggests that a lack of alcohol flushing may play a crucial role in the development of alcohol dependence in women with inactive ALDH2. No significant differences in age, usual alcohol consumption, or smoking habits were observed according to ADH1B and ALDH2 genotypes. Multiple logistic regression analyses showed that the slow-metabolizing ADH1B*1/*1 genotype (odds ratio [95% confidence interval], 12.5 [4.82–32.4] and 9.89 [3.50–27.9]), the inactive heterozygous ALDH2*1/*2 genotype (2.94 [1.18–7.38] and 3.79 [1.40–10.3]), a lower body mass index per -1 kg/m2 (1.17 [1.02–1.35] and 1.38 [1.14–1.67]), and a mean corpuscular volume ≥106 fl (3.70 [1.56–8.81] and 3.27 [1.24–8.64]) increased the risk of DIULs ≥5 mm and multiple DIULs, respectively. The combination of ADH1B*1/*1 and ALDH2*1/*2 markedly increased the risk of esophageal DIULs ≥5 mm (39.3 [10.6–146]).ConclusionsJapanese alcohol-dependent women shared several common risk factors for esophageal squamous cell neoplasia with alcohol-dependent men, but with considerably different magnitudes.

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“…The multivariate odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using multiple logistic models. We combined the ADH1B*1/*2 genotype carriers and the ADH1B*2/*2 genotype carriers into a group because of the semidominant nature of the ADH1B*2 allele . Statistical significance was defined as a P value <.05.…”

Section: Methodsmentioning

confidence: 99%

Changing trends in cancer incidence of upper aerodigestive tract and stomach in Japanese alcohol‐dependent men (1993‐2018)

2019

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Background: Esophageal squamous cell carcinoma (ESCC), head and neck SCC (HNSCC), and gastric adenocarcinoma (GA) are frequently detected at an early stage using endoscopic screening in Japanese alcohol-dependent men. Methods: We performed endoscopic screening with esophageal iodine staining and oropharyngolaryngeal inspection in 7582 Japanese alcohol-dependent men (40-79 years) during 1993-2018, and retrospectively investigated their initial screening results. Results: The 2008-2018 screening showed lower detection rates for ESCC (2.6% vs 4.0%, P = .0009) and GA (0.5% vs 1.4%, P < .0001) for all age brackets, compared with the 1993-2007 screening. The HNSCC detection rate did not change (1.0% vs 1.1%). Multiple logistic regression analyses showed that the 2008-2018 screening had a reduced OR (95% CI) for ESCC (0.34 [0.25-0.47]) and GA (0.19 [0.10-0.35]), compared with the 1993-2007 screening. The reduction in H pylori infection is probably the main reason for the decrease in GA detection over time. Declining trends in pack-years and gastric atrophy and increasing trends in age and body mass index (BMI) were found over time. The presence of advanced gastric atrophy increased the risk for ESCC as well as GA. The inactive heterozygous aldehyde dehydrogenase-2*1/*2 genotype was a strong risk factor for ESCC, HNSCC, and GA. Fewer pack-years and a larger BMI decreased the ESCC risk. However, these confounders cannot fully explain why the incidence of ESCC has decreased markedly over the recent decade. Conclusions: The detection rates of ESCC and GA have markedly decreased during the past decade in the alcohol-dependent population. The enigmatic declining trend of ESCC warrants research on this topic. K E Y W O R D S alcohol dependence, aldehyde dehydrogenase-2, chronic atrophic gastritis, esophageal cancer, gastric cancer, head and neck cancer 838 |

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Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver

Abstract: Functional correlations of ADH1B2 and ALDH22 variant alleles in the liver provide a biochemical genetic basis suggesting their contribution toward variability in ethanol metabolism as well as susceptibility to alcoholism and alcohol-related diseases in East Asians.

Cited by 16 publications

References 50 publications

Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Endoscopic screening using esophageal iodine staining and genotypes of ADH1B and ALDH2 in Japanese alcohol-dependent women

Changing trends in cancer incidence of upper aerodigestive tract and stomach in Japanese alcohol‐dependent men (1993‐2018)

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Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver

Abstract: Functional correlations of ADH1B*2 and ALDH2*2 variant alleles in the liver provide a biochemical genetic basis suggesting their contribution toward variability in ethanol metabolism as well as susceptibility to alcoholism and alcohol-related diseases in East Asians.

Cited by 16 publications

References 50 publications

Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Endoscopic screening using esophageal iodine staining and genotypes of ADH1B and ALDH2 in Japanese alcohol-dependent women

Changing trends in cancer incidence of upper aerodigestive tract and stomach in Japanese alcohol‐dependent men (1993‐2018)

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Abstract: Functional correlations of ADH1B2 and ALDH22 variant alleles in the liver provide a biochemical genetic basis suggesting their contribution toward variability in ethanol metabolism as well as susceptibility to alcoholism and alcohol-related diseases in East Asians.