Identification of P2Y12 single-nucleotide polymorphisms and their influences on the variation in ADP-induced platelet aggregation

Lee, Su-Jun; Jung, Il-Sun; Jung, Eun Ji; Choi, Ji-Yeop; Yeo, Chang-Woo; Cho, Doo‐Yeoun; Kim, Yang-Weon; Lee, Sang-Seop; Shin, Jae‐Gook

doi:10.1016/j.thromres.2010.11.023

Cited by 22 publications

(14 citation statements)

References 35 publications

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“…The polymorphism of the P2Y12 receptor gene may lead to thrombosis through the influence of platelet functions 2. The present study3 confirmed that the following five sites have polymorphisms in this gene: C34T, G52T, I-C139T, i-T744C and i-ins80lA.…”

Section: Introductionsupporting

confidence: 80%

Platelet membrane receptor P2Y12 H1/H2 polymorphisms is highly associated with cerebral infarction: a case-control study

Lu¹,

Zhou²,

Zheng³

et al. 2018

NDT

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ObjectivesThis study aimed to determine the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and cerebral infarction (CI) in a Han population in North Shandong Province, People’s Republic of China.Patients and methodsA case–control study, which involved 168 nonstoke subjects (contrast group) and 152 CI patients (CI group), was conducted. The state of subjects in the CI group was validated by computed tomography or MRI. The clinical data were categorized into two groups. The data included age, gender, smoking, drinking, shrinkage pressure, diastolic blood pressure, blood glucose, cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, serum uric acid, fibrinogen and homocysteine. The polymorphisms were genotyped with PCR and restriction fragment length polymorphism analysis. The distribution characteristics of nonstoke subjects and CI patients and the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and ischemic stroke were analyzed.ResultsNo significant difference was found between the contrast group and CI group (P>0.05) in terms of age, gender composition, smoking, alcohol consumption, blood glucose, cholesterol, triglyceride, low-density protein, high-density lipoprotein cholesterol, uric acid and homocysteine. In contrast, significant differences were found between these two groups (P<0.01) in terms of SBP, DBP and plasma fibrinogen level. The genotyping revealed 112 carriers of the wild-type H1/H1 genotype and 40 carriers of the mutational H2 allele of P2Y12 H1/H2 in the CI group and 140 carriers of the wild-type H1/H1 genotype and 28 carriers of the mutational H2 allele of P2Y12 H1/H2 in the contrast group. Furthermore, the H1/H2 and H2/H2 gene frequencies (26.3%) were significantly higher in the CI group (χ2=4.440, P<0.05) than those in the contrast group (16.7%). Moreover, the frequencies of the H2 allele in the CI and contrast groups were 14.5% and 8.6%, respectively, and the difference was statistically significant (χ2=5.392, P<0.05). Multiple logistic regression analysis results revealed that factors associated with CI include systolic blood pressure and plasma fibrinogen level, which carry the −893T gene. After adjusting for potential confounding factors, the H2 allele carriers had a 1.928-fold increased risk for CI (OR=1.928, 95% confidence interval: 1.137–3.188; P=0.038) when compared with noncarriers.ConclusionThe present study found that hypertension and elevated plasma fibrinogen levels are significant risk factors for ischemic stroke and confirmed that the H1/H2 and H2/H2 genes of platelet membrane glycoprotein receptor P2Y12 are risk factors of ischemic stroke.

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Section: Introductionsupporting

confidence: 80%

Platelet membrane receptor P2Y12 H1/H2 polymorphisms is highly associated with cerebral infarction: a case-control study

Lu¹,

Zhou²,

Zheng³

et al. 2018

NDT

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“…Few studies done on different population concluded that the carriers with H2 alleles have higher propensity for CAD with maximal platelet aggregation in response to ADP (Fontana et al 2003a) (Bura et al 2006) (Cavallari et al 2007). However, on the contrary, similar studies concluded that the gene sequence variation in P2Y12 did not contribute to the risk of development of CAD in Caucasian (Smith et al 2006) (Lev et al 2007) (Zee et al 2008) (Malek et al 2008), in French (Cuisset et al 2007), in Brazilian (Schettert et al 2006), in Mexican (Isordia-Salas et al 2012, in Italian (Giusti et al 2007), and Korean population (Lee et al 2011) (Jang et al 2012). Thus, the reasons for such conflicting results may be that a combination of hemostatic gene polymorphisms may be implicated in development of CAD rather than P2Y12 as a single entity (Martinelli et al 2008) (Tang et al 2013).…”

Section: Discussionmentioning

confidence: 94%

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

et al. 2017

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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.

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“…Genetic variants associated with CYP2C19, P2Y 12 receptor, and GPIIa are associated with reduced formation of the clopidogrel active metabolite, reduced pharmacodynamic response, and reduced platelet function. [10][11][12][13][14] A thorough assessment of the impact of these genetic variants on coronary heart disease and MACE in all major ethnic populations, including those within China, is likely to provide important insights into the risks and possible Vol 57 No 5 POLYMORPHISMS IN CORONARY HEART DISEASE PATIENTS benefits of platelet-directed pharmacotherapy in relation with specific genotypes.…”

mentioning

confidence: 99%

Genotype Frequencies of CYP2C19, P2Y<sub>12</sub> and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness

et al. 2016

Int. Heart J.

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Identification of P2Y12 single-nucleotide polymorphisms and their influences on the variation in ADP-induced platelet aggregation

Cited by 22 publications

References 35 publications

Platelet membrane receptor P2Y12 H1/H2 polymorphisms is highly associated with cerebral infarction: a case-control study

Platelet membrane receptor P2Y12 H1/H2 polymorphisms is highly associated with cerebral infarction: a case-control study

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

Genotype Frequencies of CYP2C19, P2Y<sub>12</sub> and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness

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