Abstract:
AIM:A finite number of variants in the OPRM1, COMT, MC1R, ABCB1 and CYP2D6 genes has been identified to significantly modulate the effects of opioids in controlled homogenous settings. We analyzed the imprint of these variants in opioid therapy in a highly variable cohort of pain patients treated in outpatient units to test whether genotyping may play a role in this clinical setting. METHODS:In a multicenter study conducted in tertiary care outpatient pain centers, 352 patients (156 men and 196 women, aged 58.5+/- 14.6 years) treated for 1-600 months (63.4 +/- 92.4 months) with various opioids for pain of various origins were included. Genotyping was performed for all the variants reportedly modulating pain in well-defined cohorts. Association analyses focused on opioid dosing, the actual 24-h pain score on a 0-10 rating scale and the occurrence of side effects. RESULTS:The frequency of the genetic variants in the patients did not significantly differ from that in the average Caucasian population. Daily opioid doses ranged from 4 to 1750 mg oral morphine equivalents (133.4 +/- 203.2 mg) and significantly decreased in a gene dose-dependent manner with the P-glycoprotein variant ABCB1 3435C>T. Pain was rated on average at 3.7 +/- 2.6. There was a tendency towards increased pain in a gene dose-dependent manner with the mu-opioid receptor variant OPRM1 118A>G. CONCLUSION:Genetics were reflected in the outpatient pain therapy only to a modest degree. The need of outpatient therapy of pain of various causes guided by the presently known functional genetic variants cannot be convincingly concluded from the present data. Using the ABCB1 3435 genotype to predefine lower individual opioid doses barely merits the laboratory effort. If any, the results suggest that a genetics guided outpatient pain therapy may be based on ABCB1 and OPRM1 variants.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Lötsch J,von Hentig N,Freynhagen R,Griessinger N,Zimmermann M,Doehring A,Rohrbacher M,Sittl R,Geisslinger Gdoi
10.1097/fpc.0b013e32832b89dasubject
Has Abstractpub_date
2009-06-01 00:00:00pages
429-36issue
6eissn
1744-6872issn
1744-6880journal_volume
19pub_type
临床试验,杂志文章,多中心研究abstract:OBJECTIVE:A genome-wide association study has identified several gene polymorphisms associated with loss of renal function. The effect of these variants on renal function in kidney transplant recipients receiving immunosuppressive treatment is unknown. MATERIALS AND METHODS:A cohort of 189 kidney transplant recipients...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000251
更新日期:2017-01-01 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:OBJECTIVES:To assess the influence of individual methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase A2756G polymorphisms on the change of serum folate concentration in response to different dosages and durations of folic acid (FA) supplementation in hypertensive Chinese adults. METHODS:A total o...
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.0b013e32834ac5e8
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVES:Multiple sclerosis (MS) is a neurodegenerative chronic inflammatory. Mutations in the vitamin D receptor (VDR) gene can substantially affect serum vitamin D levels or alter its functionality, and can consequently increase susceptibility to developing MS. The objective of this study was to evaluate the associ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000420
更新日期:2021-02-01 00:00:00
abstract:OBJECTIVE:Lung cancer, particularly the non-small-cell lung cancer (NSCLC) subtype, is the leading cause of cancer-related death worldwide. Several functional polymorphisms in inflammatory cytokine genes, such as IL1B, IL6, IL12A, IL13 and IL16, have been associated with the risk of NSCLC. The aim of this study was to ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000307
更新日期:2017-12-01 00:00:00
abstract::We have identified the ATP-binding cassette (ABC) transporter ABCC4 as an active constituent of mediator-storing granules in human platelets. In addition to multidrug resistance protein 4, other ABC-type transport proteins may contribute to platelet secretory function as well as determine intended or adverse effects o...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833997b0
更新日期:2010-06-01 00:00:00
abstract::The 1976C>T polymorphism in the adenosine A2A receptor gene (ADORA2A) modulates the psychological response to administration of the adenosine receptor antagonist caffeine. We quantified the vascular response to adenosine and caffeine to determine the relevance of this variant allele in the physiological response to th...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32803fb78f
更新日期:2007-07-01 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:OBJECTIVE:Identification of biomarkers that could predict gemcitabine efficacy and toxicity is a key issue in the development of individualized therapy. The aim of our study was to evaluate the influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma (MM). METHODS:In ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834e3572
更新日期:2012-01-01 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::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
abstract:OBJECTIVE:To investigate the utility of statistical tools in translating Affymetrix Drug Metabolizing Enzyme and Transporter (DMET) Assay single-nucleotide polymorphisms (SNPs) into common consensus star alleles. METHODS:DMET SNP data from clinical trials in different ethnicities were pooled for analyses. Three differ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000047
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:Clinical response to antipsychotic medications can vary markedly in patients with schizophrenia. Identifying genetic variants associated with treatment response could help optimize patient care and outcome. To this end, we carried out a large-scale candidate gene study to identify genetic risk factors predict...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000122
更新日期:2015-04-01 00:00:00
abstract::A possible association between the combination of genetic variations in hepatocyte nuclear factor 4α (HNF4α) and constitutive androstane receptor (CAR) and the stable doses of warfarin was examined in patients from the Ewha-Severance Treatment (EAST) Group of Warfarin. Around 42.5% of the overall interindividual varia...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000103
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND/AIMS:Several single-nucleotide polymorphisms (SNPs) in the catechol-O-methyltransferase (COMT) gene have been associated with the risk of developing Parkinson's disease (PD). We conducted a systematic review and a meta-analysis including all the studies published on PD risk related with COMT SNPs (mainly rs4...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,meta分析,评审
doi:10.1097/FPC.0000000000000056
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVE:We evaluated whether percent time in target range (PTTR), risk of over-anticoagulation [international normalized ratio (INR)>4], and risk of hemorrhage differ by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on the risk of hemorrhage by race. PARTICIPANTS AN...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000298
更新日期:2017-10-01 00:00:00
abstract:OBJECTIVE:Exemestane is a third-generation aromatase inhibitor used in the treatment of breast cancer in postmenopausal women. Reduction to form 17-dihydroexemestane and subsequent glucuronidation to exemestane-17-O-glucuronide is a major pathway for exemestane metabolism. The goal of this study was to analyze 17-dihyd...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833b04af
更新日期:2010-10-01 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
abstract::The existence of genetic polymorphisms in metabolizing enzymes can be regarded as one of the principal causes of interindividual variation in response to drugs and adverse reactions. In the case of enzyme CYP2C9, the presence of genetic coding variants could be considered a risk factor for suffering from gastrointesti...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,评审
doi:10.1097/FPC.0b013e328346d2bb
更新日期:2011-07-01 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::Aberrations in ubiquitin pathway have been implicated in many diseases and drug response. In a previous study on rheumatoid arthritis (RA) in Japanese population, significant association of Cullin1 gene (CUL1), an ubiquitin E3 ligase, was observed. CUL1 also mediates degradation of IκBα and p27, levels of which has be...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3283492af7
更新日期:2011-09-01 00:00:00
abstract:OBJECTIVES:Among serotonin (5-HT) receptors, the 5-HT3 receptor is the only ligand-gated ion channel. 5-HT3 antagonists such as ondansetron and tropisetron may improve auditory gating and neurocognitive deficits in schizophrenic patients. Moreover, many antipsychotic drugs are antagonists at 5-HT3 receptors. However, t...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0b013e3283313296
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Although several studies have shown that drug metabolizing enzyme gene polymorphisms may influence the impact of therapy in childhood leukemia, no comprehensive investigations have been carried out in children with neuroblastoma. The aim of this study was to identify polymorphisms in the genes encoding phase...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3280e1cc92
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:P-glycoprotein (P-gp) is a multidrug efflux transporter that has a defined role in the absorption and disposition of drugs. Many studies have investigated the potential influence of ABCB1 polymorphisms on the disposition of its substrates. However, there remains significant controversy regarding the role of ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328360d10c
更新日期:2013-06-01 00:00:00
abstract::UGT1A1 is induced by phenobarbital. We investigated whether three common UGT1A1 variants are associated with the variability in UGT1A1 inducibility. Human hepatocytes were incubated with 2 mM phenobarbital for 2 and 6 days followed by 5 microM SN-38 (1 h), a UGT1A1 probe. SN-38 glucuronidation in the cell media was me...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000182784.77630.48
更新日期:2006-02-01 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: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:To advance our understanding of disease biology, the characterization of the molecular target for clinically proven or new drugs is very important. Because of its simplicity and the availability of strains with individual deletions in all of its genes, chemogenomic profiling in yeast has been used to identify...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32835aa888
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to investigate whether there is a genotype-by-treatment interaction in patients experiencing stroke and treated with one of three antihypertensive drugs, that is chlorthalidone, amlodipine, or lisinopril. PARTICIPANTS AND METHODS:A population of 436 African Americans and 539 whites ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000088
更新日期:2014-11-01 00:00:00
abstract::Rapid development in the annotation of human genetic variation has increased the numbers of single nucleotide polymorphisms (SNPs) in candidate genes by several orders of magnitude. The selection of both useful target SNPs for disease-gene association studies and SNPs associated with the treatment response is therefor...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000194422.12770.fb
更新日期:2006-03-01 00:00:00