Abstract:
OBJECTIVES:It has been shown that acetaldehyde is an active metabolite of ethanol with central actions that modulate behavior. Catalase has been proposed as the main enzyme responsible for the synthesis of acetaldehyde from ethanol in the brain. Recent studies, however, suggest that cytochrome, in particular the isoform P450 2E1, can also contribute to the central metabolism of ethanol. METHODS:Cytochrome P4502E1 knockout (KO) mice were used to assess the involvement of this isoenzyme in some of the acute and chronic behavioral effects of ethanol. Ethanol-induced locomotion, locomotor sensitization, and voluntary ethanol intake were evaluated in cytochrome P4502E1 KO mice and their wild-type (WT) counterparts. RESULTS:Spontaneous locomotion in KO mice was lower than that seen in the WT mice. Acute administration of ethanol (1.5 g/kg, intraperitoneally) increased locomotion to a similar extent in both strains of mice. Repeated intermittent administration of ethanol produced sensitization in both strains, but it was very subtle in the KO mice compared with the effect in the WT mice. KO mice showed a reduction in preference for ethanol intake at low concentrations (4-8% v/v). Interestingly, western blot for catalase in the brain and liver showed that KO mice had higher levels of catalase expression compared with WT mice. CONCLUSION:These results show some impact of the mutation on ethanol-induced sensitization and on voluntary ethanol preference. The lack of a substantial impact of the mutation can be explained by the fact that the KO animals have a compensatory increase in catalase expression compared with WT mice, therefore possibly showing alterations in the formation of acetaldehyde after ethanol administration.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Correa M,Viaggi C,Escrig MA,Pascual M,Guerri C,Vaglini F,Aragon CM,Corsini GUdoi
10.1097/FPC.0b013e328324e726subject
Has Abstractpub_date
2009-03-01 00:00:00pages
217-25issue
3eissn
1744-6872issn
1744-6880journal_volume
19pub_type
杂志文章abstract:OBJECTIVE:Individual differences in drug efficacy and toxicity remain an important clinical concern. We investigated copy number variation (CNV) frequencies for pharmacogenes using The Cancer Genome Atlas dataset. MATERIALS AND METHODS:One hundred and fifty-two pharmacogenes were selected from liver hepatocellular car...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000097
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:Corticotropin-releasing hormone receptor (CRHR)-2 participates in smooth muscle relaxation response and may influence acute airway bronchodilator response to short-acting beta2-agonist treatment of asthma. We aim to assess associations between genetic variants of CRHR2 and acute bronchodilator response in ast...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FPC.0b013e3282fa760a
更新日期:2008-05-01 00:00:00
abstract::The present study aimed to determine whether a polymorphism in CYP3A5, encoding the major CYP3A enzyme in the human kidney, is associated with blood pressure in Caucasians. A homogenous group of 115 young, white male students with normal or mildly elevated, but untreated blood pressure was included. Blood pressure was...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000175599.49764.98
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVES:This study investigated the involvement of ADH4 gene polymorphisms in the susceptibility to alcohol use disorders. METHODS:Thirty-eight single-nucleotide polymorphisms (SNPs) in and around the ADH4 gene were investigated in 136 Italian alcoholics and 276 healthy controls. A new approach based on a bioinform...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834d05c8
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVE:Nicotine, the main addictive ingredient in tobacco, is metabolically inactivated to cotinine primarily by the hepatic enzyme CYP2A6. Considerable genetic variation in the CYP2A6 gene results in large variation in the rates of nicotine metabolism, which in turn alters smoking behaviours (e.g. amount of cigaret...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000026
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:To examine the hypothesis that genetic variation in enzymes and transporters associated with synthesis, storage, release, and metabolism of catecholamines contributes to the interindividual variability in plasma catecholamine concentrations at rest and after exercise. METHODS:We measured plasma norepinephrin...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328350a274
更新日期:2012-04-01 00:00:00
abstract:OBJECTIVES:The emergency department (ED) is a challenging setting to conduct pharmacogenomic studies and integrate that data into fast-paced and potentially life-saving treatment decisions. Therefore, our objective is to present the methods and feasibility of a pilot pharmacogenomic study set in the ED that measured pe...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000414
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND/OBJECTIVES:The zeta-1 family isoform of GST biotransforms the investigational drug dichloroacetate (DCA) and certain other halogenated carboxylic acids. Haplotype variability in GSTZ1 influences the kinetics and, possibly, the toxicity of DCA. DCA metabolism correlates with expression of the GSTZ1 protein, s...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000129
更新日期:2015-05-01 00:00:00
abstract::The genetically polymorphic cytochrome P450 2C9 (CYP2C9) metabolizes many important drugs. Among them, phenytoin has been used as a probe to determine CYP2C9 phenotype by measuring the urinary excretion of its major metabolite, S-enantiomer of 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). Phenytoin pharmacokinetic i...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000174787.92861.91
更新日期:2005-11-01 00:00:00
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journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328335731c
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVES:Prolonged activation of the β-1 adrenergic receptor (ADRB1) is associated with receptor desensitization. This process has been suggested to have important pathophysiological and clinical implications in conditions such as congestive heart failure. The contribution of genetic factors to this process is a subj...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000338
更新日期:2018-06-01 00:00:00
abstract:OBJECTIVES:To analyze whether gene variants leading to impaired drug metabolism are related with acute gastrointestinal bleeding after nonsteroidal anti-inflammatory drugs (NSAID) use. METHODS:Common CYP2C8 and CYP2C9 polymorphisms were studied in a cross-sectional study, involving 134 NSAID-related bleeding patients ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3282f305a9
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVE:To assess the impact of CYP2C9 variation on phenytoin patient response and clinician prescribing practice where genotype was unknown during treatment. METHODS:A retrospective analysis of Resource on Genetic Epidemiology Research on Adult Health and Aging cohort participants who filled a phenytoin prescriptio...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000383
更新日期:2019-10-01 00:00:00
abstract::We investigated the effect of the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to interferon-β (IFN-β) therapy in Croatian and Slovenian patients with multiple sclerosis (MS). A total of 275 IFN-β treated MS patients [162 responders (Rs) and 113 nonre...
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doi:10.1097/FPC.0000000000000283
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Organic anion transporting polypeptides (OATPs) are emerging as major determinants of pharmacokinetics for numerous drugs, with the 1B1 isoform-mediating hepatic uptake. The 521 T>C polymorphism has been correlated earlier with higher plasma concentrations of several drugs and the aim of this study was to de...
journal_title:Pharmacogenetics and genomics
pub_type: 临床试验,杂志文章
doi:10.1097/FPC.0b013e3283402efb
更新日期:2010-12-01 00:00:00
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journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01213011-200501000-00002
更新日期:2005-01-01 00:00:00
abstract::Two recent screens for copy-number variations in the entire human genome found 12.4 gene copy number variations per person, including 2.5% of individuals with gains between 7q21.1 and 7q22.1, the chromosomal location of CYP3A4. CYP3A4 is involved in the metabolism of approximately 50% of all drugs, including many canc...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000194421.35641.70
更新日期:2006-06-01 00:00:00
abstract:OBJECTIVE:The effects of various polymorphisms in cytochrome P450 (CYP) enzyme and transporter genes on the pharmacokinetics (PK) of simvastatin were evaluated in healthy Korean men. METHODS:Plasma concentration data for simvastatin and simvastatin acid were pooled from four phase I studies comprising 133 participants...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0000000000000176
更新日期:2015-12-01 00:00:00
abstract::Genome-wide studies have identified single nucleotide polymorphisms associated with smoking behaviour and nicotine dependence. Less is known about genetic determinants of smoking cessation, but rs4680 in COMT has recently been shown to explain a substantial proportion of the variation in cessation in the general popul...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32832fabf3
更新日期:2009-08-01 00:00:00
abstract::The serotonin (5-HT) 1A receptor has been found to be dysregulated in prefrontal cortex and other brain regions in schizophrenia, and 5-HT1A receptor levels in the amygdala have been related to negative schizophrenia symptoms. We have assessed the impact of the functional C-1019G variant of the 5-HT1A receptor on the ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0b013e328311a917
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:5-Hydroxytryptamine 3 (5-HT3) receptors mediate the fast excitatory neurotransmission of serotonin. In this study, we have characterized the effects of four naturally occurring, nonsynonymous variants of the human 5-HT3B subunit on expression and signalling properties of heteromeric 5-HT3AB receptors. METHO...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328310f950
更新日期:2008-12-01 00:00:00
abstract:OBJECTIVES:The effect of rifapentine plus isoniazid on efavirenz pharmacokinetics was characterized in AIDS Clinical Trials Group protocol A5279 (NCT01404312). The present analyses characterize pharmacogenetic interactions between these drugs, and with nevirapine. METHODS:A subset of HIV-positive individuals receiving...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000417
更新日期:2021-01-01 00:00:00
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doi:10.1097/FPC.0000000000000310
更新日期:2017-11-01 00:00:00
abstract:PURPOSE:Polymorphisms in genes encoding subunits of heterotrimeric G proteins have been repeatedly associated with various cancers. As G beta gamma signaling is presumed to be involved in proliferation and invasion processes, we analyzed genetic variations in regulatory regions of GNB4, which encodes the G beta 4 subun...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3283117d79
更新日期:2008-11-01 00:00:00
abstract::Asthma is the leading chronic disease in children. Several studies have identified genetic biomarkers associated with susceptibility and severity in both adult and pediatric cases. In this study, we evaluated outcomes in 400 African American and European American pediatric cases all of whom were regular users of inhal...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000355
更新日期:2018-11-01 00:00:00
abstract::Recent investigations suggest genetic susceptibility of allopurinol-induced severe cutaneous adverse reactions (SCARs). However, the strength of association was variable according to phenotypes and ethnic backgrounds. To explore genetic markers for allopurinol-induced SCARs in Koreans, we genotyped human leukocyte ant...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834282b8
更新日期:2011-05-01 00:00:00
abstract:OBJECTIVES:A total of 2402 patients with arsenic-related skin lesions, such as hyperkeratosis, hyperpigmentation or hypopigmentation, or even skin cancer in a few villages in Southwest Guizhou Autonomous Prefecture, China represent a unique case of endemic arsenism related with indoor combustion of high arsenic coal. T...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000230415.82349.4b
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:GW320659, a highly selective neuronal norepinephrine and dopamine re-uptake inhibitor, has been evaluated for the treatment of obesity. Scrutiny of the weight loss data from a phase II study (GlaxoSmithKline study OBS20001) showed a wide variation in weight loss response following GW320659 treatment and the ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/01213011-200512000-00006
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Pharmacogenetic research has shown that genetic variation may influence statin responsiveness. Statins exert a variety of beneficial effects beyond lipid lowering, including antithrombotic effects, which contribute to the risk reduction of cardiovascular disease. Statins have been shown to influence the expr...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/fpc.0b013e32832933b7
更新日期:2009-05-01 00:00:00
abstract:OBJECTIVE:As no single nucleotide polymorphism has emerged as pivotal to predict the lack of efficacy and dose-limiting toxicities to methotrexate (MTX), we evaluated the contribution of gene-gene interactions to the effects of this prodrug in rheumatoid arthritis. METHODS:A total of 255 patients treated with MTX for ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833315d1
更新日期:2009-12-01 00:00:00