ADH1B - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

ADH1B

The Experts below are selected from a list of 13967556 Experts worldwide ranked by ideXlab platform

ADH1B – Free Register to Access Experts & Abstracts

Shih-jiun Yin – One of the best experts on this subject based on the ideXlab platform.

  • Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver: phenotypic traits of the ADH1B*2 and ALDH2*2 variant gene alleles.
    Pharmacogenetics and genomics, 2016
    Co-Authors: Chien-ping Chiang, Gar-yang Chau, Shiaopieng Lee, Ching-long Lai, Wan-lin Hsu, Yu-chou Chi, Hong-wei Gao, Chung-tay Yao, Shih-jiun Yin
    Abstract:

    OBJECTIVE Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for the metabolism of ethanol. East Asian populations are unique in that they carry both a prevalent ADH1B*2 and a dominant-negative ALDH2*2 allele. A systematic investigation of ethanol-metabolizing activities in normal livers correlated with the corresponding functional allelic variations and protein contents of the relevant isozymes in respective enzyme families has been lacking. MATERIALS AND METHODS To obtain a reasonable sample size encompassing all possible genetic allelotypes of the ADH1B and ALDH2, 141 surgical liver specimens from adult Han Chinese were studied. Expression patterns and activities of ADH and ALDH were determined with stratification of the genetic phenotypes. Absolute protein contents as well as cellular localization of the activity and protein of ADH/ALDH isozymes were also investigated. RESULTS The activities of ADH1B*1/*2 and ADH1B*2/*2 allelic phenotypes were 5-6-fold those of the ADH1B*1/*1, suggesting that ADH1B*2 allele-encoded subunits are dominant over expression of hepatic ADH activity. The activities of the ALDH2-active phenotype were 90% higher than those of the ALDH2-inactive phenotype. Sex and age did not significantly influence the hepatic ADH and ALDH activities with specified genetic phenotypes. The isozyme protein contents were as follows in decreasing order: ADH1, ADH2, ALDH1A1, ALDH2, and ADH3. Both ADH1, but not ADH2/3, and ALDH1A1/2 showed a preferential expression in perivenular hepatocytes. CONCLUSION 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.

  • aldh2 2 but not ADH1B 2 is a causative variant gene allele for asian alcohol flushing after a low dose challenge correlation of the pharmacokinetic and pharmacodynamic findings
    Pharmacogenetics and Genomics, 2014
    Co-Authors: Giia-sheun Peng, Ching-long Lai, Yi-chyan Chen, Ming-fang Wang, Shih-jiun Yin
    Abstract:

    OBJECTIVE It has been well documented that variant alleles of both ADH1B*2 of alcohol dehydrogenase (ADH) and ALDH2*2 of aldehyde dehydrogenase (ALDH) protect against the development of alcoholism in East Asians. However, it remains unclear whether ADH1B*2 contributes significantly toward the accumulation of systemic blood acetaldehyde and whether it plays a critical role in the alcohol flushing reaction. PARTICIPANTS AND METHODS Sixty-one adult Han Chinese men were recruited and divided into six combinatorial genotypic groups: ALDH2*1/*1-ADH1B*1/*1 (12), ALDH2*1/*1-ADH1B*1/*2 (11), ALDH2*1/*1-ADH1B*2/*2 (11); ALDH2*1/*2-ADH1B*1/*1 (9), ALDH2*1/*2-ADH1B*1/*2 (9), and ALDH2*1/*2-ADH1B*2/*2 (9). After ingesting 0.3 g/kg of alcohol, blood ethanol, acetaldehyde, and acetate concentrations, as well as the facial skinskin blood flow (FSBF) and pulse rate were measured for 130 min. RESULTS The ALDH2*1/*2 heterozygotes carrying three ADH1B allelotypes showed significantly higher peak levels and areas under the concentration curve (AUCs) of the blood acetaldehyde as well as significantly greater increases in the peak pulse rate and peak FSBF compared with the ALDH2*1/*1 homozygotes. However, no significant differences in peak levels and AUCs of blood ethanol, acetaldehyde or acetate, or the peak cardiovascular responses, were found between the ADH1B allelotypes carrying ALDH2*1/*1 or between those with ALDH2*1/*2. Partial correlation analyses showed that peak blood acetaldehyde, rather than the blood ethanol or acetate, was correlated significantly with the peak responses of pulse rate and FSBF. CONCLUSION Findings indicate that ALDH2*2, rather than ADH1B2*2, is a causal variant allele for the accumulation of blood acetaldehyde and the resultant facial flushing during low alcohol consumption.

  • ALDH2*2 but not ADH1B*2 is a causative variant gene allele for Asian alcohol flushing after a low-dose challenge: correlation of the pharmacokinetic and pharmacodynamic findings.
    Pharmacogenetics and genomics, 2014
    Co-Authors: Giia-sheun Peng, Ching-long Lai, Yi-chyan Chen, Ming-fang Wang, Shih-jiun Yin
    Abstract:

    OBJECTIVE It has been well documented that variant alleles of both ADH1B*2 of alcohol dehydrogenase (ADH) and ALDH2*2 of aldehyde dehydrogenase (ALDH) protect against the development of alcoholism in East Asians. However, it remains unclear whether ADH1B*2 contributes significantly toward the accumulation of systemic blood acetaldehyde and whether it plays a critical role in the alcohol flushing reaction. PARTICIPANTS AND METHODS Sixty-one adult Han Chinese men were recruited and divided into six combinatorial genotypic groups: ALDH2*1/*1-ADH1B*1/*1 (12), ALDH2*1/*1-ADH1B*1/*2 (11), ALDH2*1/*1-ADH1B*2/*2 (11); ALDH2*1/*2-ADH1B*1/*1 (9), ALDH2*1/*2-ADH1B*1/*2 (9), and ALDH2*1/*2-ADH1B*2/*2 (9). After ingesting 0.3 g/kg of alcohol, blood ethanol, acetaldehyde, and acetate concentrations, as well as the facial skinskin blood flow (FSBF) and pulse rate were measured for 130 min. RESULTS The ALDH2*1/*2 heterozygotes carrying three ADH1B allelotypes showed significantly higher peak levels and areas under the concentration curve (AUCs) of the blood acetaldehyde as well as significantly greater increases in the peak pulse rate and peak FSBF compared with the ALDH2*1/*1 homozygotes. However, no significant differences in peak levels and AUCs of blood ethanol, acetaldehyde or acetate, or the peak cardiovascular responses, were found between the ADH1B allelotypes carrying ALDH2*1/*1 or between those with ALDH2*1/*2. Partial correlation analyses showed that peak blood acetaldehyde, rather than the blood ethanol or acetate, was correlated significantly with the peak responses of pulse rate and FSBF. CONCLUSION Findings indicate that ALDH2*2, rather than ADH1B2*2, is a causal variant allele for the accumulation of blood acetaldehyde and the resultant facial flushing during low alcohol consumption.

Éva Remenyik – One of the best experts on this subject based on the ideXlab platform.

  • The prevalence of ADH1B and OPRM1 alleles predisposing for alcohol consumption are increased in the Hungarian psoriasis population
    Archives of Dermatological Research, 2019
    Co-Authors: Zita Szentkereszty-kovács, Szilvia Fiatal, Andrea Szegedi, Dóra Kovács, Eszter Janka, Krisztina Herszényi, Péter Holló, Pernilla Nikamo, Mona Ståhle, Éva Remenyik
    Abstract:

    Alcohol intake affects in great the symptoms and life of  psoriasis patients, although the association of SNPs related to increased alcohol consumption with psoriasis has not been elucidated. Therefore, to investigate the association of psoriasis with established alcohol consumption and dependence-related gene variants we conducted a population-based case–control study including 3743 subjects (776 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 23 SNPs at ADH1B, ADH1C, ALDH1A1, ALDH2, SLC6A3, DDC, GABRA2, GABRG1, HTR1B, MAOA, TPH2, CHRM2, GRIN2A, POMC, OPRM1, OPRK1 and BDNF were determined and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Analysis revealed association between C allele of the rs1229984 polymorphism ( ADH1B gene) and psoriasis risk (OR_additive = 1.58, 95% CI 1.23–2.03, p  

  • the prevalence of ADH1B and oprm1 alleles predisposing for alcohol consumption are increased in the hungarian psoriasis population
    Archives of Dermatological Research, 2019
    Co-Authors: Zita Szentkeresztykovacs, Szilvia Fiatal, Andrea Szegedi, Dóra Kovács, Eszter Janka, Krisztina Herszényi, Péter Holló, Pernilla Nikamo, Mona Ståhle, Éva Remenyik
    Abstract:

    Alcohol intake affects in great the symptoms and life of  psoriasis patients, although the association of SNPs related to increased alcohol consumption with psoriasis has not been elucidated. Therefore, to investigate the association of psoriasis with established alcohol consumption and dependence-related gene variants we conducted a population-based case–control study including 3743 subjects (776 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 23 SNPs at ADH1B, ADH1C, ALDH1A1, ALDH2, SLC6A3, DDC, GABRA2, GABRG1, HTR1B, MAOA, TPH2, CHRM2, GRIN2A, POMC, OPRM1, OPRK1 and BDNF were determined and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Analysis revealed association between C allele of the rs1229984 polymorphism (ADH1B gene) and psoriasis risk (ORadditive = 1.58, 95% CI 1.23–2.03, p < 0.001, ORrecessive = 1.58, 95% CI 1.22–2.04, p = 0.001). Furthermore, the G allele of rs1799971 polymorphism (OPRM1 gene) increased the risk of familial aggregation (ORadditive = 1.99, 95% CI 1.36–2.91, p < 0.001 ORdominant = 2.01, 95% CI 1.35–3.01, p < 0.001). In subgroups of psoriatic patients with history of early onset and familial aggregation effect allele ‘C’ of rs1229984 showed association in the additive and recessive models (ORadditive = 2.41, 95% CI 1.26–4.61, p < 0.01, ORrecessive = 2.42, 95% CI 1.26–4.68, p < 0.01). While effect allele ‘G’ of rs1799971 (OPRM1) also associated with increased risk of early onset and familial aggregation of psoriasis in the additive and dominant models (ORadditive = 1.75, 95% CI 1.27–2.43, p = 0.001, ORdominant = 1.82, 95% CI 1.26–2.63, p = 0.001). Our results suggest that genetically defined high-risk individuals for alcohol consumption are more common in the psoriasis population.

Howard J Edenberg – One of the best experts on this subject based on the ideXlab platform.

  • childhood adversity moderates the effect of ADH1B on risk for alcohol related phenotypes in jewish israeli drinkers
    Addiction Biology, 2015
    Co-Authors: Jacquelyn L Meyers, Howard J Edenberg, Baruch Spivak, Amos Frisch, Efrat Aharonovich, Dvora Shmulewitz, Melanie M Wall, Katherine M Keyes, Abraham Weizman, Joel Gelernter
    Abstract:

    Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes ‘maximum drinks in a day’ (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors.

  • Complex Genetics of Alcoholism
    Neurobiology of Alcohol Dependence, 2014
    Co-Authors: Howard J Edenberg, Tatiana Foroud
    Abstract:

    Genetic factors play a significant role in the risk for alcoholism, although environmental influences are also important. Alcohol use disorders are defined by symptomology and are heterogeneous, making the identification of specific genes that affect risk difficult. Several strategies have been applied to identify genes that contribute to alcoholism and alcohol-related phenotypes, including candidate gene studies, family-based linkage studies, and genome-wide association studies. Variants in the alcohol metabolizing genes ALDH2 and ADH1B confer some protection against alcohol dependence. Common variants in other genes, including ADH4 , ADH1C , GABRA2 , GABRG1 , CHRNA5 , CHRNA3 , CHRM2 , PECR , AUTS2, PDYN, OPRK1 , and KCNJ6, have been associated with alcohol dependence or other alcohol-related phenotypes. Many of these results await further replication. Meta-analysis of large datasets is ongoing and will be critical to the identification of additional loci. Sequencing approaches are underway to identify rare variants contributing to alcoholism and alcohol-related traits.

  • the genetics of alcohol metabolism role of alcohol dehydrogenase and aldehyde dehydrogenase variants
    Alcohol Research & Health, 2007
    Co-Authors: Howard J Edenberg
    Abstract:

    The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are encoded by different genes; moreover, there are variants (i.e., alleles) of some of these genes that encode enzymes with different characteristics and which have different ethnic distributions. Which ADH or ALDH alleles a person carries influence his or her level of alcohol consumption and risk of alcoholism. Researchers to date primarily have studied coding variants in the ADH1B, ADH1C, and ALDH2 genes that are associated with altered kinetic properties of the resulting enzymes. For example, certain ADH1B and ADH1C alleles encode particularly active ADH enzymes, resulting in more rapid conversion of alcohol (i.e., ethanol) to acetaldehyde; these alleles have a protective effect on the risk of alcoholism. A variant of the ALDH2 gene encodes an essentially inactive ALDH enzyme, resulting in acetaldehyde accumulation and a protective effect. It is becoming clear that noncoding variants in both ADH and ALDH genes also may influence alcohol metabolism and, consequently, alcoholism risk; the specific nature and effects of these variants still need further study.

Shoichiro Tsugane – One of the best experts on this subject based on the ideXlab platform.

  • genetic polymorphisms of ADH1B adh1c and aldh2 alcohol consumption and the risk of gastric cancer the japan public health center based prospective study
    Carcinogenesis, 2015
    Co-Authors: Akihisa Hidaka, Keitaro Matsuo, Hidemi Ito, Shizuka Sasazuki, Norie Sawada, Taichi Shimazu, Taiki Yamaji, Motoki Iwasaki, Manami Inoue, Shoichiro Tsugane
    Abstract:

    The association between alcohol consumption, genetic polymorphisms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) and gastric cancer risk is not completely understood. We investigated the association between ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms, alcohol consumption and the risk of gastric cancer among Japanese subjects in a population-based, nested, case-control study (1990-2004). Among 36 745 subjects who answered the baseline questionnaire and provided blood samples, 457 new gastric cancer cases matched to 457 controls were used in the analysis. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using logistic regression models. No association was observed between alcohol consumption, ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms and gastric cancer risk. However, considering gene-environmental interaction, ADH1C G allele carriers who drink ≥150 g/week of ethanol had a 2.5-fold increased risk of gastric cancer (OR = 2.54, 95% CI = 1.05-6.17) relative to AA genotype carriers who drink 0 to <150 g/week (P for interaction = 0.02). ALDH2 A allele carriers who drink ≥150 g/week also had an increased risk (OR = 2.08, 95% CI = 1.05-4.12) relative to GG genotype carriers who drink 0 to < 150 g/week (P for interaction = 0.08). To find the relation between alcohol consumption and gastric cancer risk, it is important to consider both alcohol consumption level and ADH1C and ALDH2 polymorphisms.

  • Allele frequencies of single nucleotide polymorphisms (SNPs) in 40 candidate genes for gene-environment studies on cancer: data from population-based Japanese random samples
    Journal of Human Genetics, 2003
    Co-Authors: Kimio Yoshimura, Tomoyuki Hanaoka, Shumpei Ohnami, Takashi Kohno, Teruhiko Yoshida, Hiromi Sakamoto, Shoichiro Tsugane
    Abstract:

    Knowledge of genetic polymorphisms in gene-environment studies may contribute to more accurate identification of avoidable risks and to developing tailor-made preventative measures. The aim of this study was to describe the allele frequencies of single nucleotide polymorphisms (SNPs) of select genes, which may be included in future gene-environment studies on cancer in Japan. SNP typing was performed on middle-aged Japanese men randomly selected from the general population in five areas of Japan. We genotyped and calculated allele frequencies of 153 SNPs located on 40 genes: CYP1A1, CYP1B1, CYP2C9, CYP2C19, CYP2E1, CYP17A1, CYP19A1, AHR, ESR1, ESR2, ERRRG, PGR, EPHX1, EPHX2, HSD17B2, HSD17B3, GSTM2, GSTM3, GSTT2, GSTP1, NAT1, NAT2, COMT, ADH1A, ADH1B, ADH1C, ALDH2, NOS2A, NOS3, IL1A, IL1B, OGG1, NUDT1 [MTH1], DRD2, DRD3, DRD4, SLC6A4, NR3C1 [GCCR], MTHFR, and NQO1. In the present study, the Japanese allele frequencies were verified by using nationwide population samples.

Joel Gelernter – One of the best experts on this subject based on the ideXlab platform.

  • ADH1B: From alcoholism, natural selection, and cancer to the human phenome.
    American journal of medical genetics. Part B Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2017
    Co-Authors: Renato Polimanti, Joel Gelernter
    Abstract:

    The ADH1B (Alcohol Dehydrogenase 1B (class I), Beta Polypeptide) gene and its best-known functional alleles, Arg48His (rs1229984, ADH1B*2) and Arg370Cys (rs2066702, ADH1B*3), have been investigated in relation to many phenotypic traits; most frequently including alcohol metabolism and alcohol drinking behaviors, but also human evolution, liver function, cancer, and, recently, the comprehensive human phenome. To understand ADH1B functions and consequences, we provide here a bioinformatic analysis of its gene regulation and molecular functions, literature review of studies focused on this gene, and a discussion regarding future research perspectives. Certain ADH1B alleles have large effects on alcohol metabolism, and this relationship particularly encourages further investigations in relation to alcoholism and alcohol-associated cancer to understand better the mechanisms by which alcohol metabolism contributes to alcohol abuse and carcinogenesis. We also observed that ADH1B has complex mechanisms that regulate its expression across multiple human tissues, and these may be involved in cardiac and metabolic traits. Evolutionary data strongly suggest that the selection signatures at the ADH1B locus are primarily related to effects other than those on alcohol metabolism. This is also supported by the involvement of ADH1B in multiple molecular pathways and by the findings of our recent phenome-wide association study. Accordingly, future studies should also investigate other functions of ADH1B potentially relevant for the human phenome. © 2017 Wiley Periodicals, Inc.

  • childhood adversity moderates the effect of ADH1B on risk for alcohol related phenotypes in jewish israeli drinkers
    Addiction Biology, 2015
    Co-Authors: Jacquelyn L Meyers, Howard J Edenberg, Baruch Spivak, Amos Frisch, Efrat Aharonovich, Dvora Shmulewitz, Melanie M Wall, Katherine M Keyes, Abraham Weizman, Joel Gelernter
    Abstract:

    Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes ‘maximum drinks in a day’ (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors.

  • Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans
    Human Molecular Genetics, 2006
    Co-Authors: Henry R. Kranzler, Shuang Wang, Nicholas J. Schork, Joel Gelernter
    Abstract:

    : Drug dependence (DD) is commonly co-morbid with alcohol dependence (AD). Many studies have also shown common genetic risk factors for these disorders. We previously reported associations of AD with seven alcohol dehydrogenase (ADH) genes. The present study examines the relationship between these genes and DD. We genotyped 16 markers within the ADH gene cluster and 38 unlinked ancestry-informative markers in a case-control sample of 718 individuals. All markers were consistent with Hardy-Weinberg equilibrium in controls, but some markers showed Hardy-Weinberg disequilibrium in cases (minimal P = 0.002). Genotypes of many markers were associated with DD, both before and after controlling for admixture effects (minimal P < 1.0 x 10(-6)). Diplotype trend regression analysis showed that ADH5 and ADH6 genotypes, and diplotypes at ADH1A, ADH1B, ADH1C and ADH7 (minimal P = 0.002), were associated with DD in European-Americans and/or African-Americans. This first report of an allelic association of these loci with DD provides new insight into the mechanism of genetic risk for DD. These findings, obtained using a series of powerful and reliable analytic methods, may also help to explain the high rate of co-morbidity between AD and DD.