The PEAR1 gene variant rs12041331 (G allele) was strongly associated with altered platelet function (P=2.22×10⁻⁸) and greater PEAR1 protein expression in a dose-dependent manner.
Observational (n=4,831)
Does the PEAR1 gene variant rs12041331 alter platelet aggregability and protein expression in humans?
The identification of the rs12041331 variant in the PEAR1 gene provides a genetic and mechanistic basis for inter-individual variability in platelet aggregability.
Effect estimate: ≤ 15% of total phenotypic variation
p-value: p=2.22 × 10⁻⁸
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 × 10⁻⁸) and were replicated down to the variant and nucleotide level in 835 persons of African ancestry (P = 2.31 × 10⁻²⁷) and in an independent sample of 2755 persons of European descent (P = 1.64 × 10⁻⁵). Sequencing confirmed that variation at rs12041331 accounted most strongly (P = 2.07 × 10⁻⁶) 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.
Faraday et al. (Wed,) conducted a observational in Platelet function variability (n=4,831). PEAR1 gene variant rs12041331 (G allele) vs. Non-carriers or alternative alleles was evaluated on Platelet function phenotype (≤ 15% of total phenotypic variation, p=2.22 × 10⁻⁸). The PEAR1 gene variant rs12041331 (G allele) was strongly associated with altered platelet function (P=2.22×10⁻⁸) and greater PEAR1 protein expression in a dose-dependent manner.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: