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Hui Li, Erica Toth, Nathan J Cherrington
Alcohol metabolism is a well-characterized biological process that is dominated by the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) families. Nonalcoholic steatohepatitis (NASH) is the advanced inflammatory stage of nonalcoholic fatty liver disease (NAFLD) and is known to alter the metabolism and disposition of numerous drugs. The purpose of this study was to investigate the alterations in alcohol metabolism processes in response to human NASH progression. Expression and function of ADHs, ALDHs and catalase were examined in normal, steatosis, NASH (fatty) and NASH (not fatty) human liver samples...
April 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Bhagwat Prasad, Deepak Kumar Bhatt, Katherine Johnson, Revathi Chapa, Xiaoyan Chu, Laurent Salphati, Guangqing Xiao, Caroline Lee, Cornelis Eca Hop, Anita Mathias, Yurong Lai, Mingxiang Liao, W Griffith Humphreys, Sean C Kumer, Jashvant D Unadkat
To predict the impact of liver cirrhosis on hepatic drug clearance using physiologically based pharmacokinetic (PBPK) modeling, we compared the protein abundance of various Phase I and Phase II drug metabolizing enzymes (DMEs) in S9 fractions of alcoholic (n=27) or hepatitis C (HCV, n=30) cirrhotic vs. non-cirrhotic (control) livers (n=25). The S9 total protein content was significantly lower in alcoholic or HCV cirrhotic vs. control livers (i.e., 38.3 ± 8.3, 32.3 ± 12.8 vs. 51.1 ± 20.7 mg/g liver, respectively)...
April 25, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Kuka Ishioka, Hiroyuki Masaoka, Hidemi Ito, Isao Oze, Seiji Ito, Masahiro Tajika, Yasuhiro Shimizu, Yasumasa Niwa, Shigeo Nakamura, Keitaro Matsuo
BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant ALDH2-alcohol drinking interaction and a mediation effect of ALDH2/ADH1B through alcohol drinking on gastric cancer have remained unclear. We conducted two case-control studies to validate the interaction and to estimate the mediation effect on gastric cancer...
April 3, 2018: Gastric Cancer
Stephannie Shih, Yen-Tsung Huang, Hwai-I Yang
Previous work suggested a genetic component affecting the risk of hepatocellular carcinoma (HCC) and mediation analyses have elucidated potential indirect pathways of these genetic effects. Specifically, the effects of alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase (ALDH2) genes on HCC risk vary based on alcohol consumption habits. However, alcohol consumption may not be the only mediator in the identified pathway: factors related to alcohol consumption may contribute to the same indirect pathway...
March 30, 2018: Genetic Epidemiology
Abdul Anvesh Mansoori, Subodh Kumar Jain
Background: Epidemiological research has highlighted the global burden of primary liver cancer cases due to alcohol consumption, even in a low consumption country like India. Alcohol detoxification is governed by ADH1B, ALDH2, GSTM1 and GSTT1 genes that encode functional enzymes which are coordinated with each other to remove highly toxic metabolites i.e. acetaldehyde as well as reactive oxygen species generated through detoxification processes. Some communities in the population appears to be at greater risk for development of the liver cancer due to genetic predispositions...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Erna Guo, Haotang Wei, Xiwen Liao, Yang Xu, Shu Li, Xiaoyun Zeng
Previous studies have reported that alcohol dehydrogenase (ADH) isoenzymes possess diagnostic value in gastric cancer (GC). However, the prognostic value of ADH isoenzymes in GC remains unclear. The aim of the present study was to identify the prognostic value of ADH genes in patients with GC. The prognostic value of ADH genes was investigated in patients with GC using the Kaplan-Meier plotter tool. Kaplan-Meier plots were used to assess the difference between groups of patients with GC with different prognoses...
April 2018: Oncology Letters
Joel Gelernter, Hang Zhou, Yaira Z Nuñez, Apiwat Mutirangura, Robert T Malison, Rasmon Kalayasiri
BACKGROUND: Alcohol use (both quantity and dependence) is moderately heritable, and genomewide association studies (GWAS) have identified risk genes in European, African, and Asian populations. The most reproducibly identified risk genes affect alcohol metabolism. Well-known functional variants at the gene encoding alcohol dehydrogenase B and other alcohol dehydrogenases affect risk in European and African ancestry populations. Similarly, variants mapped to these same genes and a well-known null variant that maps to the gene that encodes aldehyde dehydrogenase 2 (ALDH2) also affect risk in various Asian populations...
May 2018: Alcoholism, Clinical and Experimental Research
Satoshi Abiko, Yuichi Shimizu, Shuichi Miyamoto, Marin Ishikawa, Kana Matsuda, Momoko Tsuda, Takeshi Mizushima, Keiko Yamamoto, Shoko Ono, Takahiko Kudo, Kota Ono, Naoya Sakamoto
BACKGROUND: Metachronous multiple squamous cell carcinoma (SCC) of the esophagus and the head and neck is commonly observed in patients who have previously undergone endoscopic resection (ER) for SCC of the esophagus (ESCC). We evaluated the risk for developing metachronous SCC following ER for ESCC based on the genetic polymorphisms for alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) as well as the alcohol consumption and smoking habits. METHODS: We studied 158 patients who underwent ER for ESCC (median follow-up 80 months)...
February 8, 2018: Journal of Gastroenterology
Nadine S M Offermans, Shannon M Ketcham, Piet A van den Brandt, Matty P Weijenberg, Colinda C J M Simons
The alcohol-colorectal cancer (CRC) association may differ by sex and ADH1B and ADH1C genotypes. ADH enzymes oxidize ethanol to acetaldehyde, both of which are human carcinogens. The Netherlands Cohort Study includes 120 852 participants, aged 55-69 years at baseline (1986), and has 20.3 years follow-up (case-cohort: nsubcohort = 4774; ncases = 4597). The baseline questionnaire included questions on alcohol intake at baseline and 5 years before. Using toenail DNA, available for ~75% of the cohort, we successfully genotyped six ADH1B and six ADH1C SNPs (nsubcohort = 3897; ncases = 3558)...
March 8, 2018: Carcinogenesis
Jessica E Salvatore, Shizhong Han, Sean P Farris, Kristin M Mignogna, Michael F Miles, Arpana Agrawal
Alcohol use disorder (AUD) is a heritable complex behavior. Due to the highly polygenic nature of AUD, identifying genetic variants that comprise this heritable variation has proved to be challenging. With the exception of functional variants in alcohol metabolizing genes (e.g. ADH1B and ALDH2), few other candidate loci have been confidently linked to AUD. Genome-wide association studies (GWAS) of AUD and other alcohol-related phenotypes have either produced few hits with genome-wide significance or have failed to replicate on further study...
January 9, 2018: Addiction Biology
Mehmet Ozgur Avinçsal, Hirotaka Shinomiya, Masanori Teshima, Mie Kubo, Naoki Otsuki, Naomi Kyota, Ryohei Sasaki, Yoh Zen, Ken-Ichi Nibu
BACKGROUND: The purpose of this research was to investigate the association between alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms and hypopharyngeal squamous cell carcinoma (SCC) survival. METHODS: We genotyped ADH1B (rs1229984) and ALDH2 (rs671) single nucleotide polymorphisms (SNPs) in 85 Japanese male patients with hypopharyngeal SCC. The independent prognostic values of ADH1B-ALDH2 genotypes were analyzed by univariate and multivariate proportional hazard Cox regression, taking well-known clinical risk factors into account...
April 2018: Head & Neck
Guiling Shi, Yijia Wang, Chunze Zhang, Zhenying Zhao, Xiuying Sun, Shiwu Zhang, Jinling Fan, Cunxia Zhou, Jihong Zhang, Huijuan Zhang, Jun Liu
BACKGROUND: Colorectal cancer (CRC) is a common cancer with high morbidity and mortality. However, its molecular mechanism is not clear, nor the genes related to CRC stages. METHODS: Gene expression data in CRC and healthy colorectal tissues were obtained from gene expression omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between control and CRC (stage I, II, III, and IV), obtaining 4 DEG sets. VennPlex was utilized to find all DEGs and intersection DEGs...
February 2018: Molecular and Cellular Probes
Tae Sasakabe, Kenji Wakai, Sayo Kawai, Asahi Hishida, Mariko Naito, Sadao Suzuki, Yora Nindita, Kokichi Arisawa, Yoshikuni Kita, Megumi Hara, Nagato Kuriyama, Akie Hirata, Haruo Mikami, Isao Oze, Michiaki Kubo, Hideo Tanaka, Nobuyuki Hamajima
BACKGROUND: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. METHODS: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations...
November 25, 2017: Journal of Epidemiology
Sudakshina Ghosh, Biswabandhu Bankura, Soumee Ghosh, Makhan Lal Saha, Arup Kumar Pattanayak, Souvik Ghatak, Manalee Guha, Senthil Kumar Nachimuthu, Chinmoy Kumar Panda, Suvendu Maji, Subrata Chakraborty, Biswanath Maity, Madhusudan Das
BACKGROUND: Gastric cancer (GC) is one of the most frequently diagnosed digestive tract cancers and carries a high risk of mortality. Acetaldehyde (AA), a carcinogenic intermediate of ethanol metabolism contributes to the risk of GC. The accumulation of AA largely depends on the activity of the major metabolic enzymes, alcohol dehydrogenase and aldehyde dehydrogenase encoded by the ADH (ADH1 gene cluster: ADH1A, ADH1B and ADH1C) and ALDH2 genes, respectively. This study aimed to evaluate the association between genetic variants in these genes and GC risk in West Bengal, India...
November 22, 2017: BMC Cancer
Akira Yokoyama, Nobuhito Taniki, Sachiko Hara, Emiko Haysashi, Nobuhiro Nakamoto, Takeshi Mizukami, Katsuya Maruyama, Tetsuji Yokoyama
BACKGROUND: Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B; rs1229984, His48Arg) and aldehyde dehydrogenase-2 (ALDH2; rs671, Glu504Lys) affect body weight, body fat, and lipid metabolism in individuals with alcohol dependence, and the aim of this study was to identify their determinants in relation to the development of fatty liver. METHODS: We evaluated associations between the presence of fatty liver and ADH1B and ALDH2 genotypes and other factors in 1604 Japanese men who had been admitted for treatment of alcohol dependence...
October 23, 2017: Journal of Gastroenterology
Félix Javier Jiménez-Jiménez, Javier Gómez-Tabales, Hortensia Alonso-Navarro, Martín Zurdo, Laura Turpín-Fenoll, Jorge Millán-Pascual, Teresa Adeva-Bartolomé, Esther Cubo, Francisco Navacerrada, Ana Rojo-Sebastián, Lluisa Rubio, Mónica Díez-Fairén, Pau Pastor, Marisol Calleja, José Francisco Plaza-Nieto, Belén Pilo-de-la-Fuente, Margarita Arroyo-Solera, Esteban García-Albea, José A G Agúndez, Elena García-Martín
Background/Objectives: Several studies have raised the possibility of an association between alcohol consumption and the risk of developing restless legs syndrome (RLS). Moreover, an important percentage of patients under alcohol detoxification therapy develop RLS symptoms that fulfil the criteria for idiopathic RLS during alcohol withdrawal. We have aimed to establish the possible association between two common single nucleotide polymorphisms (SNPs) in the alcohol-dehydrogenase 1B (ADH1B) gene and the risk for RLS...
December 1, 2017: Sleep
Chung-Lieh Hung, Shun-Chuan Chang, Sheng-Hsiung Chang, Po-Ching Chi, Yu-Jun Lai, Shih-Wei Wang, Yih-Jer Wu, Hung-I Yeh, Shing-Jong Lin, Che-Hong Chen, Daria Mochly-Rosen, Li-Yu Wang
Aims: Excessive consumption of alcoholic beverages is associated with cardiac remodeling and cardiomyopathy. We examined the possible association of alcohol use, common Asian genetic variants in genes involved in alcohol metabolism, and cardiac structures/functions alterations. Methods: A prospective, community-dwelling survey among individuals with available complete echocardiography examined the associations of alcohol use, cardiac structure/functions, and three common alcohol metabolizing genetic variants, including aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) and cytochrome P450 (CYP) isoform 2E1 (CYP2E1)...
November 1, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
Yu-Feng Hu, Yao-Ting Chang, Yenn-Jiang Lin, Shih-Lin Chang, Li-Wei Lo, Yen-Hua Huang, Tze-Tze Liu, Che-Hong Chen, Ta-Chuan Tuan, Tze-Fan Chao, Fa-Po Chung, Jo-Nan Liao, Abigail Louise D Te, Chi-Ying F Huang, Shih-Ann Chen
BACKGROUND: Alcohol consumption is known to increase the risk of atrial fibrillation (AF). Whether the genotypes of alcohol-metabolizing genes (alcohol dehydrogenase [ADH1B]) are associated with the risk of AF recurrence after catheter ablation remains unclear. METHODS AND RESULTS: The ADH1B genotypes of 281 patients who received catheter ablation for AF were examined. We followed this group of patients to monitor their AF recurrence. Alcohol consumption levels of this cohort were evaluated before and after catheter ablation...
December 2017: Pacing and Clinical Electrophysiology: PACE
Stéphanie Durand, Killian Trillet, Arnaud Uguen, Aude Saint-Pierre, Catherine Le Jossic-Corcos, Laurent Corcos
BACKGROUND: Colon cancer occurrence is increasing worldwide, making it the third most frequent cancer. Although many therapeutic options are available and quite efficient at the early stages, survival is strongly decreased when the disease has spread to other organs. The identification of molecular markers of colon cancer is likely to help understanding its course and, eventually, to uncover novel genes to be targeted by drugs. In this study, we compared gene expression in a set of 95 human colon cancer samples to that in 19 normal colon mucosae, focusing on 401 genes from 5 selected pathways (Apoptosis, Cancer, Cholesterol metabolism and lipoprotein signaling, Drug metabolism, Wnt/beta-catenin)...
September 30, 2017: BMC Genomics
T-K Clarke, M J Adams, G Davies, D M Howard, L S Hall, S Padmanabhan, A D Murray, B H Smith, A Campbell, C Hayward, D J Porteous, I J Deary, A M McIntosh
Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals...
October 2017: Molecular Psychiatry
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