Important Variant Information for P2RY1
Submitted by: Katrin Sangkuhl (PharmGKB)
Reviewed by: under review
Submitted date: Mar 21, 2008
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There are Two Important Variants for P2RY1.
| Gene HGNC Name: | P2RY1 |
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| Variant Summary: | The platelet responses to antithrombotic drugs like aspirin or clopidogrel are considerably variable among individuals. To identify patients who do not derive protection from aspirin therapy, the association between SNP in four candidate genes (ITGB3, PTGS1, PTGS2, P2RY1) implicated in the platelet aggregation pathway and aspirin resistance was investigated. A group of 332 white men with a history of myocardial infarction who underwent percutaneous coronary intervention were genotyped for seven SNPs (two in the P2RY1 gene: 893C>T and 1622A>G). All patients were on an aspirin regimen with a dosage of 81 mg/day [15757620]. The study found only one polymorphism in the P2RY1 gene that was significantly associated with aspirin resistance. The C to T base substitution at position 893 (rs1065776) of the P2RY1 gene was associated with a >3-fold increase in aspirin resistance, whereas the 1622A>G polymorphism (rs701265) showed no association [15757620]. Another study aimed to evaluate the association of SNPs in PTGS1, P2RY1, and ITGB3 genes with response to aspirin in healthy Chinese volunteers. A total of 24 subjects participated in the prospective aspirin trial including seven subjects with 893CC-1622GG genotype, five subjects with 893CC-1622AG genotype, six subjects with 893CC-1622AA genotype, and six subjects with 893CT-1622AG genotype. The results showed a significantly larger reduction in mean platelet aggregation after aspirin treatment in the P2RY1 893CT-1622AG genotype versus the other three genotypic groups with an 893CC genotype background [17559347]. These finding are at odds with the study described above, which observed an increased frequency of the 893T allele in the aspirin-resistant individuals. The researchers argue that the difference in their subjects demographics and health status might contribute to this discrepancy [17559347]. Li et al. summarized the genotype frequencies of both P2RY1 polymorphisms found in the coding region of the gene [17559347]. For the 893C>T SNP, they compared their results obtained in healthy Chinese volunteers with a study on Caucasians with a history of myocardial infarction who underwent percutaneous coronary intervention [15757620]. For the 1622A>G variant, the comparative study had Caucasians with no history of coronary heart disease enrolled [15514209].
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| Key PubMed IDs: | 15757620, 17559347 |
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| Genomic Variant & GenBank ID: | 59048774 C>T on NT_005612 | ||||||||||||||||||||||||||||
| mRNA Variant & GenBank ID: | 893 C>T on NM_002563 | ||||||||||||||||||||||||||||
| Protein Variant & GenBank ID: | 19 Ala>Ala on NP_002554 | ||||||||||||||||||||||||||||
| dbSNP rs#: | rs1065776 |
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| GoldenPath Position: | chr3:154036318 (hg18) |
| Gene HGNC Name: | P2RY1 |
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| Variant Summary: | An interindividual variation in platelet response to ADP is widely observed, but the reason for this variaion in response is not well understood. Common variants in P2RY1 and P2RY12 genes were identified and the functional influence on platelet reactivity variation was investigated in 200 white participants with northern European background. The study identified five polymorphisms in the P2RY1 gene and 11 in the P2RY12 gene [15514209]. The 1622A>G SNP (rs701265) in the P2RY1 gene was found to have a significant association with platelet response to ADP. Although the polymorphism is synonymous, the effect, defined by binding of fibrinogen to activated GPIIb-IIIa, was present at all doses of ADP. According to the paper, this association might indicate a phenotypic effect. However, the translation of the elevated fibrinogen binding into increased platelet aggregation was not explained by this study. Since the 1622A>G SNP is silent, and therefore has no influence at the primary structure, the actual mechanism remains to be elucidated. One possible explanation is that the effect of the polymorphism is at the P2RY1 receptor expression level [15514209]. To investigate this further, 1000bp upstream of the P2RY1 gene has been sequenced in 13 subjects and ten additional SNP were identified. The C>T substitution at position -545 is in complete linkage disequilibrium with 1622A>G, which suggests a potential link to regulation of expression in the promoter region [15514209]. Another study investigated the 1622A>G variant with regard to a possible association with altered response to aspirin and clopidogrel [16581111]. A group of 120 patients undergoing percutaneous coronary intervention were enrolled and genotyped for polymorphisms in the P2RY1 (1622A>G variant), P2RY12 and ITGB3 gene after treatment with aspirin and clopidogrel. The responses were assessed by platelet aggregation and platelet surface expression of activation markers. No evidence was found for a significant association between these polymorphisms and the response to aspirin or clopidogrel [16581111]. |
| Key PubMed IDs: | 15514209, 16581111 |
| Genomic Variant & GenBank ID: | 59049503 A>G on NT_005612 |
| mRNA Variant & GenBank ID: | 1622 A>G on NM_002563 |
| Protein Variant & GenBank ID: | 262 Val>Val on NP_002554 |
| dbSNP rs#: | rs701265 |
| GoldenPath Position: | chr3:154037047 (hg18) |