Polymorphisms of MDR1, CYP2C19 and P2Y12 genes in Indian population: Effects on clopidogrel response

Shalia, Kavita; Shah, Vinod K.; Pawar, Poonam; Divekar, Siddhi; Payannavar, Satchidanand

doi:10.1016/j.ihj.2013.02.012

Cited by 40 publications

(46 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In Indian scenario, a study done in North Indian patients with CAD does not show any mutant genotypes for P2Y12 (i744T>C) polymorphism (Kar et al 2013). However, the study which was done on Maharashtrian, Gujarati, and Marwadi representing the western region of India showed a similar frequency distribution both in cases and controls as compared to that of the present study done in South Indian Tamilian population (Shalia et al 2013). This shows that there is significant intraethnic and interethnic variation in the distribution of variant alleles among Indians.…”

Section: Discussionsupporting

confidence: 75%

“…Henceforth, the exact role of P2Y12 polymorphism in association with CAD has to be substantially evaluated in clinical settings. Moreover, there are studies reporting the allele and genotype frequency of P2Y12 gene polymorphism in other populations (Azarpira et al 2011) (Shalia et al 2013) (Kar et al 2013), but to our knowledge, there is no data available for South Indian Tamilian population. Hence, the present study was aimed to determine the genotype and allele frequency of P2Y12 (i744T>C) gene polymorphism in the South Indian Tamilian population to predict its possible role in the development of CAD in this population.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

et al. 2017

View full text Add to dashboard Cite

Several factors contribute to the development of coronary artery disease (CAD). Adenosine diphosphate (ADP) activated P2Y12 receptor also plays a key role in platelet activation and aggregation. It has been found that common variation in the P2Y12 gene was associated with increased platelet aggregation resulting in adverse cardiovascular outcomes. Thus, polymorphisms in the ADP receptor P2Y12 may contribute to the development of CAD. This study aims to determine the frequency distribution of platelet receptor polymorphism P2Y12 (i744T>C) in Tamilian population and to predict its possible role in CAD. Three hundred seventyone subjects were recruited comprising of 221 healthy volunteers and 150 patients with CAD belonging to either sex, aged 18-60 years of Tamilian origin. Genomic DNA was extracted using phenol-chloroform method. Genotyping was done by PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism). The C allele frequency of P2Y12 polymorphism in controls and cases was 8.4% and 17.7%, respectively. The TT, TC, and CC genotype frequencies in controls and cases were 83.7%, 15.8%, 0.5% and 66.7%, 31.3%, 2%, respectively. The genotype frequencies were in HardyWeinberg equilibrium. There was a significant association (p < 0.05) between the mutant genotypes of P2Y12 (i744T>C) polymorphism and risk of CAD. The odds ratio was found to be 2.6. The variant allele frequency of P2Y12-i744T>C was significantly different from other populations. There was a significant association between the mutant genotypes of P2Y12 (i744T>C) polymorphism and risk of developing CAD. Thus, the present study will emphasize on the relevance of pharmacogenetic testing of P2Y12 (i744T>C) receptor gene polymorphism in CAD patients.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

et al. 2017

View full text Add to dashboard Cite

show abstract

“…CYP2C19*17 is associated with rapid metabolism of clopidogrel. 14 In Indian population the reported frequency CYP2C19*17 are in between 16% -35.5%. 7-10-14,15 Studies have shown that CYP2C19*17 variant is not independently associated with clopidogrel response and observed effect of this variant is due to LD with the CYP2C19*2 loss-of-function variant.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19][20][21][22] In a study by Shalia et al, have observed that poor response to clopidogrel at 24 h with the variant genotypes of CYP2C19*2 as compared to wild type. 14 In one study, it has been reported that genetic contribution accounts for only approximately 12% of the response variability to clopidogrel. 18 However, it is unknown whether the time course of the antiplatelet effects of clopidogrel differs according to CYP2C19*2 phenotype in south Indian patients with ACS.…”

Section: Introductionmentioning

confidence: 99%

Association of Polymorphisms in CYP2C19 with the Efficacy of Clopidogrel Therapy in South Indian Patients Undergoing Percutaneous Coronary Intervention

Kumari¹,

Ravella²,

Kumar³

et al. 2017

JCDR

View full text Add to dashboard Cite

Background:The dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been considered as the standard of care in the setting of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). Recent evidence supports a role of loss-of-function (LOF) variants in the CYP2C19 as a determinant of clopidogrel response. Carriers of the CYP2C19*2 LOF allele has found to have the reduced pharmacodynamic response to clopidogrel and worse clinical outcome as compared with non-carriers in Asian countries including Indian population. However, it is unknown whether the time course of the antiplatelet effects of clopidogrel differs according to CYP2C19 genotype in South Indian patients with ACS. Methods: We assessed the platelet reactivity in the early and late phases of ACS according to CYP2C19 genotypes. Eighty six consecutive in-patients who were admitted with ACS at our center were enrolled in the study. The determination of platelet aggregation was done by using a platelet aggregometer and genetic analysis was done by PCR-RFLP method. Results: The numbers of patients carrying the CYP2C19*1/*1 (extensive metabolizer, EM), *1/*2 (Intermediate metabolizer, IM), *2/*2 (poor metabolizer PM), genotypes were 22 (30.9%), 37 (52.1%), 12 (16.9%), respectively. Time course of platelet aggregation from baseline to the late phase among the 3 genotypes indicate that there was statistically significant at 30 th day of treatment (p=0.004) between wild versus hetero and homozygous variant alleles. The percentage of patients shifted to prasugrel from clopidogrel due to non-response were 4 (8%), 11(29%), 6 (50%) in wild, heterozygous and homozygous variant alleles. In homozygous group, we found 4 out of 6 patients developed acute stent thrombosis within one week of PCI. Conclusion: We observed that the CYP2C19*2 and CYP2C19*1/*2 are the major determinants of clopidogrel efficacy. Acute stent thrombosis was observed in patients carrying CYP2C19*2 variant allele

show abstract

“…Several single nucleotide polymorphisms (SNPs) in the ABCB1 gene have been identified as candidates for CHD susceptibility; among them, C3435T (rs1045642 C > T) is the most common variant that has been widely investigated (Chowbay et al, 2005;Bournissen et al, 2009;Haerian et al, 2010). Recently, many studies have indicated that ABCB1 C3435T polymorphism might play a critical role in increasing CHD risk (Simon et al, 2009;Wallentin et al, 2010;Shalia et al, 2013). However, there is also some evidence that ABCB1 C3435T polymorphism had no effect on susceptibility to CHD (Poduri et al, 2009;Spiewak et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

ABCB1 C3435T Polymorphism and the Risk of Coronary Heart Disease: A Meta-Analysis

Jin

Wang

et al. 2014

Genetic Testing and Molecular Biomarkers

View full text Add to dashboard Cite

show abstract

Polymorphisms of MDR1, CYP2C19 and P2Y12 genes in Indian population: Effects on clopidogrel response

Abstract: The present study did show a trend toward impaired response of clopidogrel to inhibit platelet aggregation with variant genotypes of CYP2C19*2 and iT744C of P2Y12 compared to respective wild type genotype at 24 h.

Cited by 40 publications

References 35 publications

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

Association of Polymorphisms in CYP2C19 with the Efficacy of Clopidogrel Therapy in South Indian Patients Undergoing Percutaneous Coronary Intervention

ABCB1 C3435T Polymorphism and the Risk of Coronary Heart Disease: A Meta-Analysis

Contact Info

Product

Resources

About