Abstract:
OBJECTIVE:Methotrexate (MTX) is an important drug in the treatment of pediatric acute lymphoblastic leukemia (ALL). MTX is cytotoxic as it impairs DNA and RNA synthesis by inhibiting the enzymes dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS). The association between genetic variants within the TYMS gene and MTX-induced toxicity has been studied, but results are inconsistent. We determined the role of three previously described variants within the TYMS gene and MTX-induced oral mucositis in a prospective cohort of Dutch children with ALL and performed a meta-analysis of the previous results. MATERIALS AND METHODS:We analyzed the presence of a 28-base pair tandem repeat (rs34743033; 2R3R), a single nucleotide polymorphism present within the 28-base pair repeat on the 3R allele (rs2853542; 3RG>C) and a 6-base pair deletion (rs15126436; TTAAAG) within the TYMS gene in germline DNA of 117 pediatric patients with ALL. Oral mucositis was defined as grade≥3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. Data were analyzed for the individual rs34743033 (2R3R) and rs151264360 (6 bp deletion) polymorphisms, whereas rs2853542 (3RG>C) was combined with rs34743033 (2R3R) and analyzed according to predicted expression levels of TYMS: low expression (2R/2R, 2R/3RC and 3RC/3RC), median expression (2R/3RG and 3RC/3RG) and high expression (3RG/3RG). We performed a meta-analysis of the current literature on these polymorphisms in relation to oral mucositis using a fixed effects model. RESULTS:The 2R2R genotype (rs34743033) was not significantly associated with developing MTX-induced oral mucositis compared with the 2R3R/3R3R genotypes, which was confirmed in a meta-analysis [odds ratio (OR): 1.17 (0.62-2.19)]. Patients carrying the low-expression TYMS genotype (2R2R, 2R3RC, 3RC3RC) had an increased odds of developing MTX-induced oral mucositis [OR: 2.42 (0.86-6.80)], which did not reach statistical significance. The 6-bp deletion [rs151264360, OR: 0.79 (0.20-3.19)] was not associated with the development of MTX-induced oral mucositis. CONCLUSION:The TYMS 6-bp deletion and 2R3R polymorphism were not associated with MTX-induced oral mucositis. Validation studies in prospective cohorts are necessary to assess the possible role of the low-expression TYMS genotypes in relation to MTX-induced oral mucositis.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Oosterom N,Berrevoets M,den Hoed MAH,Zolk O,Hoerning S,Pluijm SMF,Pieters R,de Jonge R,Tissing WJE,van den Heuvel-Eibrink MM,Heil SGdoi
10.1097/FPC.0000000000000352subject
Has Abstractpub_date
2018-10-01 00:00:00pages
223-229issue
10eissn
1744-6872issn
1744-6880journal_volume
28pub_type
杂志文章,meta分析abstract::Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed fo...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833de489
更新日期:2010-10-01 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:Paraoxonase-1 (PON1) is synthesized in the liver and is bound to high-density lipoprotein particles in blood. PON1 protects against the development of atherosclerosis by metabolizing proatherogenic-oxidized lipids. The Southeastern USA (excluding Florida) has the country's highest age-adjusted mortality rate ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834cebc6
更新日期:2011-12-01 00:00:00
abstract::Several novel single nucleotide polymorphisms (SNPs) involved in cytarabine cytotoxicity and related to clinical outcomes have been reported recently in a series of 232 pediatric patients with acute myeloid leukemia (AML). We report the first adult AML cohort in which the influence of these SNPs in cytarabine efficacy...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000286
更新日期:2017-07-01 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:OBJECTIVE:Glutathione S-transferase enzymes (GSTs; EC: 2.5.1.18) constitute the principal phase II superfamily, which plays a key role in cellular detoxification. GST genes are organized in chromosomal clusters; most of these genes are polymorphic, mainly due to single nucleotide substitutions. Different studies proved...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328349da4d
更新日期:2011-10-01 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::P-glycoprotein, the product of the ABCB1 gene, is a proposed mechanism of pharmacoresistance in epilepsy. Previous attempts to correlate the ABCB1 C3435T SNP, or a three-SNP haplotype containing C3435T with epilepsy pharmacoresistance have produced discordant findings. We analysed these single nucleotide polymorphisms...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,meta分析
doi:10.1097/01.fpc.0000230408.23146.b1
更新日期:2007-03-01 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 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::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: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::Fumaric acid esters (FAE) are beneficial in the treatment of psoriasis. However, about a third of psoriasis patients do not respond to FAE. We aimed to determine whether glutathione-S-transferase (GST) M1 and GSTP1 polymorphisms are associated with treatment outcome in psoriasis patients treated with FAE. We studied 8...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000218
更新日期:2016-05-01 00:00:00
abstract:OBJECTIVES:We tested the effect of kidney-specific multidrug resistance-related protein (MRP2, ABCC2) deficiency on renal organic solute disposition as well as on renal protein and gene expression. Furthermore, we investigated whether a particular kidney donor ABCC2 genotype is associated with delayed graft function in...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328328d4e9
更新日期:2009-04-01 00:00:00
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::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::Carboxylesterase 1 (CES1) is implicated in the metabolism of several commonly used drugs and other xenobiotics. The gene encoding this enzyme, CES1, is duplicated in some individuals. The original gene copy is called CES1A1. The duplicated version, CES1A2, is a hybrid of CES1A1 and the CES1-related pseudogene, CES1P1....
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000267
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVE:The objective of the present study was to evaluate whether germline methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms as well as polymorphisms in the thymidylate synthase gene promoter, namely the variable number tandem repeat polymorphism (TS VNTR) and the intrarepeat G to C single n...
journal_title:Pharmacogenetics and genomics
pub_type: 临床试验,杂志文章
doi:10.1097/01.fpc.0000230412.89973.c0
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVE:Irreversible hearing loss is a frequent side effect of the chemotherapeutic agent cisplatin and shows considerable interpatient variability. The variant rs1872328 in the ACYP2 gene was recently identified as a risk factor for the development of cisplatin-induced ototoxicity in children with brain tumors. We a...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000212
更新日期:2016-05-01 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) is a key regulator of the transcriptional expression for the cytochrome P450 1 (CYP1) genes. CYP1A2 is one of the major CYP1 enzymes that catalyse 2-hydroxylation of estrogen, a hormone that plays a critical role in the etiology of breast cancer. In this study, we investigated wheth...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000189803.34339.ed
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:The prototypical atypical antipsychotic agent, clozapine, is more efficacious for refractory schizophrenia than the 'typical' antipsychotics, but the mechanism underlying this enhanced efficacy is still under investigation. Since 2002, at least 22 association studies have shown that the DTNBP1 can be associat...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0b013e32832b9cfc
更新日期:2009-06-01 00:00:00
abstract:OBJECTIVES:The development of targeted drugs would greatly benefit from the simultaneous identification of biomarkers to determine the aspects of bioactivity, drug safety and efficacy, particularly when affecting receptor-signaling pathways. However, the establishment of appropriate systems to monitor drug-induced even...
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:OBJECTIVE:To determine whether polymorphisms in the sulfonamide detoxification genes, CYB5A (encoding cytochrome b(5)), CYB5R3 (encoding cytochrome b(5) reductase), or NAT2 (encoding N-acetyltransferase 2) were over-represented in patients with delayed sulfonamide drug hypersensitivity, compared with control patients w...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328357a735
更新日期:2012-10-01 00:00:00
abstract:RATIONALE:Selecting an effective treatment for patients with major depressive disorder is a perpetual problem for psychiatrists. It is of particular interest to explore the interaction between genetic predisposition and environmental factors. OBJECTIVES:Mouse inbred strains vary in baseline performance in depression-r...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834b3f35
更新日期:2011-12-01 00:00:00
abstract:OBJECTIVE:Niacin has been used for seven decades to modulate plasma lipids, but its mechanism of action is still unclear. We sought to determine whether variants in the niacin receptor gene, hydroxyl-carboxylic receptor 2 (HCAR2), are associated with lipid response to treatment. PARTICIPANTS AND METHODS:Coding variant...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0000000000000289
更新日期:2017-08-01 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::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:We investigated whether the UGT1A3 polymorphisms play an important role in interindividual variations in atorvastatin lactonization and lipid-lowering effect. METHODS:Twenty-three healthy volunteers were administered atorvastatin 20 mg once daily for 14 days. Serum levels of lipids were measured before and 7...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3283544085
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to examine the associations between genetic variations in the human KCNK2 gene and major depressive disorder (MDD) and response to antidepressant treatment. METHOD:Four hundred and forty-nine patients with MDD and 421 normal controls were included in the study; among the MDD patient...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32832cbe61
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVE:To describe the usage patterns of antidepressants with published CYP2D6- and CYP2C19-based prescribing guidelines among depressed primary care patients and estimate the proportion of patients taking antidepressants not recommended for them based on their CYP2C19 and CYP2D6 genotype-predicted metabolizer statu...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000406
更新日期:2020-09-01 00:00:00