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Q Zhong, R R Wu, Z M Zeng
Human colorectal cancer (CRC) is a major worldwide health concern, and its development has been shown to be associated with alcohol intake. We carried out a study to investigate the effect of the ADH1B Arg47His and ALDH2 Glu487Lys genetic polymorphisms and their interaction with alcohol consumption on development of CRC. Between March 2013 and May 2015, a total of 274 CRC patients and 358 healthy controls were recruited. Genotyping of sequence variations was performed using the polymerase chain reaction-restriction fragment length polymorphism method...
September 23, 2016: Genetics and Molecular Research: GMR
Daxu Li, Ruizhi Zhang, Tianbo Jin, Na He, Le Ren, Zhe Zhang, Qingna Zhang, Ran Xu, Hong Tao, Guang Zeng, Jing Gao
In this study, we assessed the association between single nucleotide polymorphisms (SNPs) in candidate genes and the prognosis of laryngeal cancer (LC) patients. Thirty-seven SNPs in 26 genes were genotyped in 170 male Han Chinese patients with LC. The effects of the candidate genes on the prognosis of LC patients were evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. The GA genotype of rs1229984 (hazard ratio [HR], 0.537; 95% confidence interval [CI], 0.340-0.848; p = 0.008) in alcohol dehydrogenase 1B (ADH1B), and the AA genotype of rs9929218 (HR, 6...
September 28, 2016: Oncotarget
Yu-Chou Chi, Shou-Lun Lee, Ching-Long Lai, Yung-Pin Lee, Shiao-Pieng Lee, Chien-Ping Chiang, Shih-Jiun Yin
Alcohol dehydrogenase (ADH) is the principal enzyme responsible for metabolism of ethanol. Human ADH constitutes a complex isozyme family with striking variations in kinetic function and tissue distribution. Liver and gastrointestinal tract are the major sites for first-pass metabolism (FPM). Their relative contributions to alcohol FPM and degrees of the inhibitions by aspirin and its metabolite salicylate, acetaminophen and cimetidine remain controversial. To address this issue, mathematical organ modeling of ethanol-oxidizing activities in target tissues and that of the ethanol-drug interactions were constructed by linear combination of the corresponding numerical rate equations of tissue constituent ADH isozymes with the documented isozyme protein contents, kinetic parameters for ethanol oxidation and the drug inhibitions of ADH isozymes/allozymes that were determined in 0...
October 25, 2016: Chemico-biological Interactions
C Menni, S Metrustry, G Ehret, A F Dominiczak, P Chowienczyk, T D Spector, S Padmanabhan, A M Valdes
OBJECTIVE: The dicarboxylic fatty acid hexadecanedioate is functionally associated with increased blood pressure. The aims of this study was to further characterize which pathways are related to this compound using genetic and transcriptomic data. DESIGN AND METHOD: A genome-wide association scan (GWAS) was conducted on 6447 individuals from the TwinsUK and KORA cohorts. SNPs achieving genome-wide significance were then tested in the International Consortium for Blood Pressure and in a GWAS of extremes of blood pressure...
September 2016: Journal of Hypertension
Ning Mao, Siyao Nie, Bin Hong, Chao Li, Xueyuan Shen, Tao Xiong
BACKGROUND: It has been shown that gene polymorphisms may play an important role in the carcinogenesis of esophageal cancer. This study is to investigate the role of alcohol dehydrogenase 1B (ADH1B) gene Arg47His polymorphism in esophageal cancer susceptibility. METHODS: Case-control studies published between January 2000 and June 2015 were searched to retrieve relevant articles. The pooled odds ratio (OR) and 95 % confidence interval (CI) were employed to calculate the strength of association...
2016: World Journal of Surgical Oncology
Cassie Yu, Jon McClellan
Substance abuse disorders have a strong genetic component. Genetic risk factors associated with alcohol abuse include common variants in genes coding for alcohol-metabolizing enzymes and gamma-aminobutyric acid A receptors. Functional missense mutations in ADH1B and ALDH2 are protective against alcohol dependence. Nicotine use disorders are associated with polymorphisms in a cluster of nicotinic acetylcholine receptors on chromosome 15q24, and mutations that reduce the enzymatic activity of CYP2A6. Genetic risk factors for other illicit drug use have not been well-studied...
July 2016: Child and Adolescent Psychiatric Clinics of North America
Guang Yin, Mariko Naito, Kenji Wakai, Emi Morita, Sayo Kawai, Nobuyuki Hamajima, Sadao Suzuki, Yoshikuni Kita, Toshiro Takezaki, Keitaro Tanaka, Makiko Morita, Hirokazu Uemura, Etsuko Ozaki, Satoyo Hosono, Haruo Mikami, Michiaki Kubo, Hideo Tanaka
Associations between alcohol consumption and type 2 diabetes risk are inconsistent in epidemiologic studies. This study investigated the associations of ADH1B and ALDH2 polymorphisms with fasting blood glucose levels, and the impact of the associations of alcohol consumption with fasting blood glucose levels in Japanese individuals. This cross-sectional study included 907 men and 912 women, aged 35-69 years. The subjects were selected from among the Japan Multi-institutional Collaborative Cohort study across six areas of Japan...
May 2016: Nagoya Journal of Medical Science
E S Kuznetsova, O L Zinovieva, N Yu Oparina, M M Prokofjeva, P V Spirin, I A Favorskaya, I B Zborovskaya, N A Lisitsyn, V S Prassolov, T D Mashkova
Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors...
March 2016: Molekuliarnaia Biologiia
Renato Polimanti, Henry R Kranzler, Joel Gelernter
To identify novel traits associated with alleles known to predispose to alcohol and nicotine use, we conducted a phenome-wide association study (PheWAS) in a large multi-population cohort. We investigated 7688 African-Americans, 1133 Asian-Americans, 14 081 European-Americans, and 3492 Hispanic-Americans from the Women's Health Initiative, analyzing alleles at the CHRNA3-CHRNA5 locus, ADH1B, and ALDH2 with respect to phenotypic traits related to anthropometric characteristics, dietary habits, social status, psychological traits, reproductive history, health conditions, and nicotine/alcohol use...
October 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Zhanlong Shen, Bo Wang, Jianyuan Luo, Kewei Jiang, Hui Zhang, Harri Mustonen, Pauli Puolakkainen, Jun Zhu, Yingjiang Ye, Shan Wang
UNLABELLED: Lysine acetylated modification was indicated to impact colorectal cancer (CRC)'s distant metastasis. However, the global acetylated proteins in CRC and the differential expressed acetylated proteins and acetylated sites between CRC primary and distant metastatic tumor remains unclear. Our aim was to construct a complete atlas of acetylome in CRC and paired liver metastases. Combining high affinity enrichment of acetylated peptides with high sensitive mass spectrometry, we identified 603 acetylation sites from 316 proteins, among which 462 acetylation sites corresponding to 243 proteins were quantified...
June 16, 2016: Journal of Proteomics
Karen G Chartier, Danielle M Dick, Laura Almasy, Grace Chan, Fazil Aliev, Marc A Schuckit, Denise M Scott, John Kramer, Kathleen K Bucholz, Laura J Bierut, John Nurnberger, Bernice Porjesz, Victor M Hesselbrock
OBJECTIVE: Variations in the genes encoding alcohol dehydrogenase (ADH) enzymes are associated with both alcohol consumption and dependence in multiple populations. Additionally, some environmental factors have been recognized as modifiers of these relationships. This study examined the modifying effect of religious involvement on relationships between ADH gene variants and alcohol consumption-related phenotypes. METHOD: Subjects were African American, European American, and Hispanic American adults with lifetime exposure to alcohol (N = 7,716; 53% female) from the Collaborative Study on the Genetics of Alcoholism...
May 2016: Journal of Studies on Alcohol and Drugs
Tamara L Wall, Susan E Luczak, Susanne Hiller-Sturmhöfel
Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects...
2016: Alcohol Research: Current Reviews
Akira Yokoyama, Yoko Kamada, Hiromi Imazeki, Emiko Hayashi, Shigenori Murata, Kenji Kinoshita, Tetsuji Yokoyama, Yoshinori Kitagawa
BACKGROUND: The genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol (sEtOH) levels are well correlated with blood EtOH levels. METHODS: To study the effects of ADH1B and ALDH2 genotypes on the alcohol elimination rate (AER) and salivary acetaldehyde (sAcH) levels, we measured the sEtOH and sAcH levels twice at a 1-hour intervals in 99 intoxicated Japanese alcoholic men who had stopped drinking for 4 or more hours...
June 2016: Alcoholism, Clinical and Experimental Research
Janne Schurmann Tolstrup, Marie Kim Wium-Andersen, David Dynnes Ørsted, Børge Grønne Nordestgaard
BACKGROUND: The aim of this study was to test the hypothesis that alcohol consumption, both observational (self-reported) and estimated by genetic instruments, is associated with a risk of atrial fibrillation and to determine whether people with high cardiovascular risk are more sensitive towards alcohol than people with low risk. METHODS: We used data for a total of 88,782 men and women from the Copenhagen City Heart Study 1991-1994 and 2001-2003 and the Copenhagen General Population Study 2003-2010...
September 2016: European Journal of Preventive Cardiology
Eléonore A Attignon, Alix F Leblanc, Béatrice Le-Grand, Caroline Duval, Martine Aggerbeck, Hélène Rouach, Etienne B Blanc
The mechanisms by which pollutants participate in the development of diverse pathologies are not completely understood. The pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates the AhR (aryl hydrocarbon receptor) signaling pathway. We previously showed that TCDD (25 nM, 30 h) decreased the expression of several alcohol metabolism enzymes (cytochrome P450 2E1, alcohol dehydrogenases ADH1, 4 and 6) in differentiated human hepatic cells (HepaRG). Here, we show that, as rapidly as 8 h after treatment (25 nM TCDD) ADH expression decreased 40 % (p < 0...
April 8, 2016: Archives of Toxicology
Kenichi Kagemoto, Yuji Urabe, Tomohiro Miwata, Shiro Oka, Hidenori Ochi, Yasuhiko Kitadai, Shinji Tanaka, Kazuaki Chayama
A previous genome-wide association study identified two novel esophageal squamous cell carcinoma (ESCC) susceptibility genes, ADH1B and ALDH2. We investigated the characteristics of ESCC, and the relationship between metachronous esophageal and/or pharyngeal squamous cell carcinoma (SCC) and the ADH1B & ALDH2 risk alleles. One hundred and seventeen superficial ESCC patients who underwent treatment with endoscopic submucosal dissection (ESD) were followed up using endoscopy for ≥12 months. First, we performed a replication analysis to confirm the relationship between ESCC and the ADH1B & ALDH2 risk alleles using 117 superficial ESCC cases and 1125 healthy controls...
July 2016: Cancer Medicine
Shigenori Murata, Mariko Hayashida, Yuko Ishiguro-Tanaka, Hiromi Imazeki, Emiko Hayashi, Akira Yokoyama, Kenji Kinoshita
We have developed a new method for unprocessed biological specimens as templates directly into the TaqMan assay. Saliva was needed to be put on a water-soluble paper and dried, because foreign substances, such as a filter paper, hinder fluorescence detection through the assay. Genotyping of alcohol metabolism-related genes ADH1B (rs1229984) and ALDH2 (rs671) polymorphisms was, subsequently, performed by TaqMan PCR assay using dried saliva in the present investigation. The optimized technique was tested on 114 samples of alcoholic patients...
November 2015: Rinsho Byori. the Japanese Journal of Clinical Pathology
Hiroyuki Masaoka, Hidemi Ito, Norihito Soga, Satoyo Hosono, Isao Oze, Miki Watanabe, Hideo Tanaka, Akira Yokomizo, Norio Hayashi, Masatoshi Eto, Keitaro Matsuo
Although a range of chemical exposures (cigarette smoking and occupational exposure) are recognized risk factors for the development of bladder cancer (BCa), many epidemiological studies have demonstrated that alcohol drinking is not associated with BCa risk. Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms impact the accumulation of acetaldehyde, resulting in an increased risk of various cancers. To date, however, no studies evaluating the association between BCa risk and alcohol drinking have considered these polymorphisms...
June 2016: Carcinogenesis
Neelanjana Roy, Debanjali Dasgupta, Indranil Mukhopadhyay, Ankita Chatterjee, Kausik Das, Pradip Bhowmik, Soumyajit Das, Priyadarshi Basu, Amal K Santra, Simanti Datta, Gopal Krishna Dhali, Abhijit Chowdhury, Soma Banerjee
Genetic susceptibility is an important modifier of clinical outcome and natural history of progression in Alcoholic liver disease (ALD). While the significance of ethnicity in this evolution is very clear, subtle inter-individual genetic variant(s) might be important and thus we investigated those in an Indian population. Fourteen markers were genotyped within two alcohol metabolism genes [Alcohol dehydrogenase (ADH) gene clusters (ADH1B and ADH1C) and Aldehyde dehydrogenase (ALDH2)], one microsomal ethanol oxidizing enzyme cytochrome p450 (CYP2E1) and three oxidative stress response (OSR) genes (MnSOD, GSTT1 and GSTM1) among 490 Bengali individuals (322 ALD and 168 control) from Eastern and North-Eastern India and validation was performed in a new cohort of 150 Bengali patients including 100 ALD and 50 advanced non-alcoholic steatohepatitis (NASH)...
2016: PloS One
Kevin J Galinsky, Gaurav Bhatia, Po-Ru Loh, Stoyan Georgiev, Sayan Mukherjee, Nick J Patterson, Alkes L Price
Searching for genetic variants with unusual differentiation between subpopulations is an established approach for identifying signals of natural selection. However, existing methods generally require discrete subpopulations. We introduce a method that infers selection using principal components (PCs) by identifying variants whose differentiation along top PCs is significantly greater than the null distribution of genetic drift. To enable the application of this method to large datasets, we developed the FastPCA software, which employs recent advances in random matrix theory to accurately approximate top PCs while reducing time and memory cost from quadratic to linear in the number of individuals, a computational improvement of many orders of magnitude...
March 3, 2016: American Journal of Human Genetics
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