Carriage of Cytochrome 2C19 Polymorphism Is Associated With Risk of High Post-Treatment Platelet Reactivity on High Maintenance-Dose Clopidogrel of 150 mg/day

Jeong, Young‐Hoon; Kim, In-Suk; Park, Yongwhi; Kang, Min-Kyung; Koh, Jin‐Sin; Hwang, Seok-Jae; Kwak, Choong Hwan; Hwang, Jin‐Yong

doi:10.1016/j.jcin.2010.05.007

Cited by 84 publications

(54 citation statements)

References 38 publications

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“…Several articles have reported an increase in adverse outcomes in both poor and intermediary metabolizers treated with standard doses of clopidogrel. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Two large meta-analyses have confirmed these findings. 18,19 A promoter variant *17 causes increased CYP2C19 activity and is classified as an ultrarapid metabolizer allele.…”

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confidence: 81%

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

Strom

Goos

Crossley

et al. 2012

Genetics in Medicine

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Purpose:We sought to determine the genotype frequencies for cytochrome p450 enzyme 2C19 variant alleles both in the US panethnic population and various US ethnic groups and to establish the frequency of clinically actionable genotypes. methods:Analytical results were obtained from 1,396 consecutive samples submitted for cytochrome p450 enzyme 2C19 genotyping tests and stored in a proprietary database. This database was queried and genotypes and predicted phenotypes established. Anonymized samples were obtained from specimens submitted for cystic fibrosis genotyping that contained ethnicity information. Samples from 357, 149, and 346 individuals self-identified as white, African American, and Hispanic, respectively, were analyzed. In addition, 342 anonymized samples submitted for Ashkenazi Jewish panel testing were analyzed.Results: Significant ethnic differences were observed in the frequencies of the *17 ultrarapid allele among the various groups studied. In the pan-ethnic population, 3.8% of tested patients were classified as ultrarapid metabolizers, 24% as extensive metabolizers heterozygous for a *17 ultrarapid allele, 27% as intermediate metabolizers, and 3.5% as poor metabolizers. Using stringent criteria, 7.3% of individuals would have clinically actionable genotypes. In addition, we detected two individuals with a haplotype of *2/*17 and a single individual with a haplotype of *4/*17 indicating that the *17 hypermetabolic allele can occur on a *1, *2, or *4 background.Genet Med 2012:14(1):95-100

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confidence: 81%

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

Strom

Goos

Crossley

et al. 2012

Genetics in Medicine

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“…9 However, other studies indicated the limited influence that high-dose clopidogrel has in normalizing platelet reactivity in patients carrying the LoF allele and that the antiplatelet effect of 150 mg/d clopidogrel was negligible in poor metabolizers. 43,44 The largest (nϭ1152) combined assessment of genotype and serial platelet function was reported in a recent substudy of the GRAVITAS trial. In that analysis, the CYP2C19 LoF allele was significantly associated with high post-PCI platelet reactivity during high-dose clopidogrel treatment (odds ratioϭ1.62 for 1 LoF and 11.2 for 2 LoF alleles).…”

Section: Addressing the Problem Of Cyp2c19 Lof Allele Carriage: High-mentioning

confidence: 99%

Platelet Function Testing and Genotyping Improve Outcome in Patients Treated With Antithrombotic Agents

2012

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“…In comparison, the loss of 1 allele results in partially compromised platelet aggregation post-clopidogrel treatment (Mega et al, 2009;Chen et al, 2010;Jeong et al, 2010;Pettersen et al, 2011). Another form, CYP2C19*17, has been implicated in bleeding following clopidogrel treatment (Sibbing et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Diversity of platelet function and genetic polymorphism in clopidogrel-treated Chinese patients

Sun¹,

Li²,

Ming³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We investigated the correlation between genetic polymorphisms of cytochrome P450 enzyme genes and the outcome of clopidogrel treatment in 118 coronary disease patients after percutaneous coronary intervention at the Chinese PLA General Hospital. Patients were divided into an ischemia event relapse group (IERG) and a non-IERG group (NIERG) based on relapse of ischemia events within 6 months after percutaneous coronary intervention. Ischemia occurred in 26.27% of patients. Thromboelastogram platelet mapping results showed that compared with the NIERG, the ADP-induced platelet inhibition ratio in the IERG was significantly lower (31.33 ± 24.91% vs 54.68 ± 26.63%, P < 0.05). The platelet inhibition ratio of patients carrying mutant alleles CYP3A5*3 (41.98 ± 29.33% vs 52.89 ± 26.49%), CYP2C19*2 (43.15 ± 27.97% vs 55.89 ± 26.71%), and P2Y12*1 (38.74 ± 24.36% vs 52.19 ± 28.58%) was lower than patients with the wild-type alleles. The frequency of ischemia event relapse in patients 1435 Clopidogrel and platelet function

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Carriage of Cytochrome 2C19 Polymorphism Is Associated With Risk of High Post-Treatment Platelet Reactivity on High Maintenance-Dose Clopidogrel of 150 mg/day

Cited by 84 publications

References 38 publications

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

Platelet Function Testing and Genotyping Improve Outcome in Patients Treated With Antithrombotic Agents

Diversity of platelet function and genetic polymorphism in clopidogrel-treated Chinese patients

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