Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression.
Blood
; 118(12): 3367-75, 2011 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-21791418
ABSTRACT
Genetic variation is thought to contribute to variability in platelet function; however, the specific variants and mechanisms that contribute to altered platelet function are poorly defined. With the use of a combination of fine mapping and sequencing of the platelet endothelial aggregation receptor 1 (PEAR1) gene we identified a common variant (rs12041331) in intron 1 that accounts for ≤ 15% of total phenotypic variation in platelet function. Association findings were robust in 1241 persons of European ancestry (P = 2.22 × 10â»8) and were replicated down to the variant and nucleotide level in 835 persons of African ancestry (P = 2.31 × 10⻲7) and in an independent sample of 2755 persons of European descent (P = 1.64 × 10â»5). Sequencing confirmed that variation at rs12041331 accounted most strongly (P = 2.07 × 10â»6) for the relation between the PEAR1 gene and platelet function phenotype. A dose-response relation between the number of G alleles at rs12041331 and expression of PEAR1 protein in human platelets was confirmed by Western blotting and ELISA. Similarly, the G allele was associated with greater protein expression in a luciferase reporter assay. These experiments identify the precise genetic variant in PEAR1 associated with altered platelet function and provide a plausible biologic mechanism to explain the association between variation in the PEAR1 gene and platelet function phenotype.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
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Doença da Artéria Coronariana
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Agregação Plaquetária
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Receptores de Superfície Celular
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Polimorfismo de Nucleotídeo Único
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População Negra
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População Branca
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Estudos de Associação Genética
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article