Abstract:
OBJECTIVES:The aim of this study was to evaluate the effect of polymorphisms affecting the clopidogrel metabolism (CYP3A4 IVS10+12G/A and CYP2C19*2) and the P2Y12 receptor (P2Y12 T744C) on modulating platelet function in acute coronary syndrome patients on dual antiplatelet treatment. BACKGROUND:Residual platelet reactivity (RPR) phenomenon on antiplatelet therapy requires clarification. P2Y12 T744C, CYP3A4 IVS10+12G/A and, in healthy individuals only, CYP2C19*2 polymorphisms have been investigated; however, the influence on platelet reactivity in a large population of high-risk vascular patients on dual antiplatelet treatment has not yet been elucidated. METHODS:A total of 1419 acute coronary syndrome patients on dual antiplatelet treatment were studied. Platelet function was evaluated by platelet-rich plasma aggregation. Electronic nanochips and restriction-fragment length polymorphism were used for analysis of polymorphisms. RESULTS:Only CYP2C19*2, out of the three investigated polymorphisms, is associated with higher platelet reactivity. Carriers of the *2 allele had significantly higher platelet aggregation values after arachidonic acid (AA; P=0.043), 2 micromol/l adenosine 5' diphosphate (ADP; P<0.0001) and 10 micromol/l ADP (P=0.001) stimuli. The genotype distribution of CYP2C19*2 polymorphism significantly differed between patients with and without RPR, as evaluated by 10-micromol/l ADP-induced platelet aggregation (P=0.002) and by AA-induced platelet aggregation (P=0.045). At the multivariate linear regression analysis, the CYP2C19*2 polymorphism remained a significant and independent risk factor for dual antiplatelet treatment variability. CONCLUSIONS:This study demonstrates, for the first time, that the *2 CYP2C19 allele is associated with higher platelet aggregability and RPR in high-risk vascular patients on dual antiplatelet treatment. These findings can have a significant impact on the future design of pharmacogenetic antiaggregant strategies for high-risk vascular patients on dual antiplatelet treatment.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Giusti B,Gori AM,Marcucci R,Saracini C,Sestini I,Paniccia R,Valente S,Antoniucci D,Abbate R,Gensini GFdoi
10.1097/FPC.0b013e3282f1b2besubject
Has Abstractpub_date
2007-12-01 00:00:00pages
1057-64issue
12eissn
1744-6872issn
1744-6880pii
01213011-200712000-00006journal_volume
17pub_type
杂志文章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: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:INTRODUCTION:Cytochrome P450 1A2 (CYP 1A2) is responsible for more than 90% of caffeine clearance. A polymorphic variant of CYP1A2 (-163C>A) (rs762551) is associated with high CYP1A2 inducibility. Both caffeine and its main metabolite, paraxanthine, may be neuroprotective. The association between caffeine intake and ri...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3282f09265
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:Alcohol is detoxified in the liver by oxidizing enzymes that require nicotinamide adenine dinucleotide (NAD+) such that, in the rat, the availability of NAD+ contributes to control voluntary ethanol intake. The UChA and UChB lines of Wistar rats drink low and high amounts of ethanol respectively and differ in...
journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e32832dc12a
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abstract:OBJECTIVE:To investigate if polymorphisms of some genes involved in folliculogenesis predict ovarian response. METHODS:This prospective randomized study includes 124 egg donors genotyped for six SNPs ESR1 (rs2234693), AMHR2 (rs2002555), GDF-9 (rs10491279 and rs254286), AMH (rs10407022) and LHCBR (rs229327) genes and f...
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abstract:INTRODUCTION:Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial. OBJECTIVES:The stud...
journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e32835693f7
更新日期:2012-10-01 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...
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journal_title:Pharmacogenetics and genomics
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journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e328363176f
更新日期:2013-08-01 00:00:00
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更新日期:2008-07-01 00:00:00
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doi:10.1097/FPC.0b013e32832cbe61
更新日期:2009-10-01 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
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doi:10.1097/01.fpc.0000230409.00276.44
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journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,评审
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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
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更新日期:2007-03-01 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 ...
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更新日期:2007-08-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/01.fpc.0000174787.92861.91
更新日期:2005-11-01 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
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doi:10.1097/FPC.0b013e328360d10c
更新日期:2013-06-01 00:00:00
abstract::In humans, UDP-glucuronosyltransferase 1A9 is known to glucuronidate numerous lipophilic substances of pharmacological and toxicological importance. Although it has been established that individuals vary in their capacity to express this detoxification enzyme, little is known about the mechanisms that dictate the regu...
journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e32801112b5
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVE:Studies found a strong association between allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the HLA-B*58:01 allele. HLA-B*58:01 screening-guided therapy may mitigate the risk of allopurinol-induced SJS/TEN. This study aimed to evaluate the cost-effectiveness of HLA-B*58:...
journal_title:Pharmacogenetics and genomics
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更新日期:2018-02-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/01.fpc.0000230415.82349.4b
更新日期:2006-12-01 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
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doi:10.1097/FPC.0000000000000122
更新日期:2015-04-01 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
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doi:10.1097/FPC.0000000000000417
更新日期:2021-01-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e328328d4e9
更新日期:2009-04-01 00:00:00