ABCB1 C3435T and CYP2C19*2 polymorphisms in a Palestinian and Turkish population: A pharmacogenetic perspective to clopidogrel

Nassar, Suheir M.; Amro, Omar; Abu-Rmaileh, H; Alshaer, Inji; Korachi, May; Ayesh, Suhail

doi:10.1016/j.mgene.2014.01.009

Cited by 10 publications

(6 citation statements)

References 36 publications

(36 reference statements)

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“…Almost all previous publications concerning clopidogrel absorption variability focused on the effects of genetic polymorphism of ABCB1 on antiplatelet and PK response to clopidogrel and clinical outcomes. However, published data on the association of ABCB1 genetic variants and antiplatelet effects and PKs of clopidogrel are inconsistent . We did not find an SNP consistently associated with PRU and H4 concentration.…”

Section: Discussioncontrasting

confidence: 89%

Genomewide Association Study Identifies Novel Genetic Loci That Modify Antiplatelet Effects and Pharmacokinetics of Clopidogrel

Chen

et al. 2017

Clin Pharma and Therapeutics

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Genetic variants in the pharmacokinetic (PK) mechanism are the main underlying factors affecting the antiplatelet response to clopidogrel. Using a genomewide association study (GWAS) to identify new genetic loci that modify antiplatelet effects in Chinese patients with coronary heart disease, we identified novel variants in two transporter genes (SLC14A2 rs12456693, ATP‐binding cassette [ABC]A1 rs2487032) and in N6AMT1 (rs2254638) associated with P2Y12 reaction unit (PRU) and plasma active metabolite (H4) concentration. These new variants dramatically improved the predictability of PRU variability to 37.7%. The associations between these loci and PK parameters of clopidogrel and H4 were observed in additional patients, and its function on the activation of clopidogrel was validated in liver S9 fractions (P < 0.05). Rs2254638 was further identified to exert a marginal risk effect for major adverse cardiac events in an independent cohort. In conclusion, new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment.

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Section: Discussioncontrasting

confidence: 89%

Genomewide Association Study Identifies Novel Genetic Loci That Modify Antiplatelet Effects and Pharmacokinetics of Clopidogrel

Chen

et al. 2017

Clin Pharma and Therapeutics

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“…Both frequencies are lower than observed for Caucasians and Africans (15%) or Asians (29–35%) [17]; however, our study reports a very similar frequency to countries such as Bolivia (7.8%) [20], Colombia (8.7%) [21], and Mexico (9.7%) [22] as well as Canadian native inhabitants (8.8%) [23]. Moreover, CYP2C19 ∗ 2 MAF obtained is comparable to different African populations such as Egyptians (10.9%) [24], Tanzanians (10%) [25], and Tunisians (10.5%) [26]; European populations such as Belgians (9.1%) [27]; and also Middle Eastern populations like Iranians (11.1%) [28] and Palestinians (9%) [29]. …”

Section: Discussionmentioning

confidence: 79%

CYP2C19⁎2 Polymorphism in Chilean Patients with In-Stent Restenosis Development and Controls

Ruedlinger

Prado

Zambrano

et al. 2017

BioMed Research International

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Clopidogrel is an antiplatelet drug especially used in patients undergoing percutaneous coronary interventions (PCI). Polymorphisms within CYP2C19 can result in important interindividual variations regarding therapeutic efficacy. Therefore, we aimed to evaluate the impact of the CYP2C19⁎2 variant (rs4244285) on in-stent restenosis occurrence in Chilean patients who underwent PCI and received clopidogrel. A total of 77 cases with stenosis >50% in the angioplasty site (62.75 ± 9.8 years, 80.5% males) and 86 controls (65.45 ± 9.8 years, 72.1% males) were studied. The polymorphism was genotyped using TaqMan® Drug Metabolism Genotyping Assays. Overall, CYP2C19⁎2 allele frequency was 8.3%. Diabetes, chronic lesions, and bare metal stents (BMS) were observed more often in cases than in controls (p = 0.05, p = 0.04, and p = 0.02, resp.). Genotypic frequencies did not differ significantly between the groups (p = 0.15). Nonetheless, the mutated allele was observed in a greater proportion in patients without in-stent restenosis (p = 0.055). There was no significant association between the rs4244285 variant and the occurrence of in-stent restenosis after PCI (OR = 0.44; 95% CI: 0.19 to 1.04; p = 0.06). In summary, no association was identified between the CYP2C19⁎2 variant and the development of coronary in-stent restenosis.

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“…Hardy-Weinberg equilibrium was tested and reported in only 9 studies. 28,[30][31][32][36][37][38][39][40]…”

Section: Prevalence Of Explored Genetic Variantsmentioning

confidence: 99%

The Effect of CYP2C19 and Nongenetic Factors on Clopidogrel Responsiveness in the MENA Region: A Systematic Review

Ali

Elewa

2019

Clin Appl Thromb Hemost

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Clopidogrel is the cornerstone antiplatelet used in the treatment and prevention of thrombotic events. Some studies examined the effect of CYP2C19 polymorphism and nongenetic factors on clopidogrel response in the Middle East and North Africa (MENA) region. However, the consistency among these studies is yet unknown. This study aims to estimate the prevalence of CYP2C19 genetic variants in MENA region and to evaluate the effect of these variants as well as the nongenetic factors on clopidogrel responsiveness. A systematic literature search was performed to identify relevant articles. Only observational studies were included. A total of 20 studies in 8 different populations were included. The CYP2C19*2 variant is the most prevalent loss-of-function (LOF) allele in the MENA region (1.7%-35%). The frequency of CYP2C19*17 ranged from 5.3% to 26.9%. Of the 9 studies, 6 found an association between carriers of at least 1 LOF allele and clopidogrel resistance. Older age, high body mass index, females, and the use of calcium channel blockers were associated with clopidogrel resistance as well. Association between the CYP2C19*2 allele and clopidogrel resistance is common among MENA populations. Future studies should focus on having larger sample sizes to detect other minor variant alleles and their effect on bleeding and cardiovascular outcomes.

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ABCB1 C3435T and CYP2C19*2 polymorphisms in a Palestinian and Turkish population: A pharmacogenetic perspective to clopidogrel

Cited by 10 publications

References 36 publications

Genomewide Association Study Identifies Novel Genetic Loci That Modify Antiplatelet Effects and Pharmacokinetics of Clopidogrel

Genomewide Association Study Identifies Novel Genetic Loci That Modify Antiplatelet Effects and Pharmacokinetics of Clopidogrel

CYP2C19⁎2 Polymorphism in Chilean Patients with In-Stent Restenosis Development and Controls

The Effect of CYP2C19 and Nongenetic Factors on Clopidogrel Responsiveness in the MENA Region: A Systematic Review

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