PEAR1

Genome-wide association studies (GWAS) have successfully identified thousands of single nucleotide polymorphisms (SNPs) associated with complex traits; however, the identified SNPs account for a fraction of trait heritability, and identifying the functional elements through which genetic variants exert their effects remains a challenge. Recent evidence suggests that SNPs associated with complex traits are more likely to be expression quantitative trait loci (eQTL). Thus, incorporating eQTL information can potentially improve power to detect causal variants missed by traditional GWAS approaches...

INTRODUCTION: The interindividual variability of the antiplatelet effect of clopidogrel is determined by multiple clinical and genetic factors. A lot of genotype-oriented studies have concentrated on the impact of CYP2C19 gene polymorphisms on platelet aggregation in patients receiving clopidogrel. However, the influence of this polymorphism may be only 12-20%, so other genetic markers should also be investigated. The aim of this work was to study the impact of carriage of CES1, PON1, ABCG2, CYP4F2, CYP3A4, IGTB3, P2Y12, PEAR1, and B4GALT2 polymorphisms on antiplatelet effect of clopidogrel and clinical outcomes in patients with acute coronary syndrome (ACS) and atrial fibrillation (AF)...

Background: The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel. Methods: A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied...

This multicenter clinical study was aimed at conducting a targeted pharmacogenomic association analysis of residual on-clopidogrel platelet reactivity in 474 Caribbean Hispanic patients. Platelet reactivity was measured using the VerifyNow P2Y12 assay and clopidogrel resistance was defined as P2Y12 reaction units (PRUs) greater than or equal to 208. Genotyping was performed using the whole-genome Infinium MEGA BeadChip array. An ancestry-adjusted, weighted polygenic risk score (wPGxRS) was developed to account for the effect of multiple variants on PRU and compared between clopidogrel responders and nonresponders...

Charge interactions play a critical role in the activation of the innate immune system by damage- and pathogen-associated molecular pattern receptors. The ability of these receptors to recognize a wide spectrum of ligands through a common mechanism is critical in host defense. In this article, we argue that platelet glycoprotein receptors that signal through conserved tyrosine-based motifs function as pattern recognition receptors (PRRs) for charged endogenous and exogenous ligands, including sulfated polysaccharides, charged proteins and nanoparticles...

Stroke is one of the world's leading causes of disability and death. Antiplatelet agents are administered to acute ischemic stroke patients as secondary prevention. Clopidogrel involves biotransformation by cytochrome P450 (CYP) enzymes into an active metabolite, and single nucleotide polymorphisms (SNPs) can influence the efficacy of this biotransformation. Despite the therapeutic advantages of aspirin, there is significant inter-individual heterogeneity in response to this antiplatelet drug. In this clinical review, the recent advances in the biomarkers of antiplatelet agents in acute ischemic stroke are discussed...

Background: Platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 has been reported to affect agonist-stimulated platelet aggregation, but it remains unclear whether this variant plays a role in recurrent stroke. Here we assess the clinical relevance of PEAR1 rs12041331 in acute minor ischemic stroke (AMIS) and transient ischemic attack (TIA) Chinese patients treated with dual antiplatelet therapy (DAPT). Methods: We recruited 273 consecutive minor stroke and TIA patients, and Cox proportional hazard regression was used to model the relationship between PEAR1 rs12041331 and thrombotic and bleeding events...

Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets...

Aim: The aim of this study was to assess the association between PEAR1  polymorphisms and ischemic clinical outcomes. Materials & methods: We searched the electronic database for articles on the relationship of PEAR1 SNPs and ischemic events in patients with coronary artery disease (CAD) up to October 2020. Results: A total of 9914 patients with CAD from six studies focusing on 12 SNPs of PEAR1 were included in this study. The A allele of rs12041331 were associated with ischemic events (odds ratio: 1...

All participants were administered with oral aspirin (100 mg/d) for 7 days. Blood samples were then collected and platelet function evaluated by an automated PL-12 analyzer, TEG, and the platelet count drop method. We found that platelet counts determined by the traditional platelet drop method were significantly lower in the PL-12 sensitive group and significantly higher in the PL-12 insensitive group (P < 0.05). Furthermore, MAR measured by PL-12 was positively correlated with the MA values determined by TEG and the platelet drop method (r = 0...

Leukemia cell-intrinsic somatic mutations and cytogenetic abnormalities have been used to define risk categories in acute myeloid leukemia (AML). In addition, since the immune microenvironment might influence prognosis and somatic mutations have been demonstrated to modulate the immune microenvironment in AML, there is need for developing and evaluating an immune prognostic model (IPM) derived from mutations associated with poor prognosis. Based on AML cases with intermediate and adverse-cytogenetic risk in the Cancer Genome Atlas (TCGA) database, 64 immune-related differentially expressed genes (DEGs) among patients with RUNX1, TP53, or ASXL1 mutations and patients without these mutations were identified...

Platelet Endothelial Aggregation Receptor 1 (PEAR1) is an orphan receptor of unknown function which mediates powerful activation of platelets and endothelial cells in response to crosslinking by antibodies and sulfated polysaccharides belonging to the dextran and fucoidan families. PEAR1 is a single transmembrane protein composed of 15 epidermal growth factor-like repeat sequences and with a conserved binding motif, YXXM, which when phosphorylated binds to phosphoinositide 3-kinase (PI3K). The 13th of the repeats has a heparin-binding sequence that is the site of interaction with the sulfated fucoidans and the only known endogenous ligand FcεRIα...

Newly discovered Erwinia amylovora phages PEar1, PEar2, PEar4 and PEar6 were isolated from three different orchards in North Tunisia to study their potential as biocontrol agents. Illumina sequencing revealed that the PEar viruses carry a single-strand DNA genome between 6608 and 6801 nucleotides and belong to the Inoviridae, making them the first described filamentous phages of E. amylovora . Interestingly, phage-infected cells show a decreased swimming and swarming motility and a cocktail of the four phages can significantly reduce infection of E...

The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. We undertook post hoc analysis of 13,547 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, median age 74 years...

BACKGROUND The purpose of this study was to investigate factors influencing bleeding in patients with acute coronary syndrome (ACS) who are on aspirin and ticagrelor as dual antiplatelet therapy. MATERIAL AND METHODS This retrospective case-control study included 50 patients with ACS (25 with reported bleeding events and 25 without) on aspirin and ticagrelor. Adenosine diphosphate (ADP)- and arachidonic acid (ACA)-induced platelet aggregation rates were measured using light transmission aggregometry. Single-nucleotide polymorphisms (SNPs) in PEAR1, GP1BA, and GSTP1 were genotyped...

Platelet Endothelial Aggregation Receptor (PEAR1), as a platelet receptor, plays a vital role in hemostasis. This receptor, by its extracellular part, causes platelet adhesion and consequently initiates platelet aggregation. Dysfunction of PEAR1 can disrupt platelet aggregation in patients with cardiovascular diseases (CVDs). The content used in this paper has been taken from English language articles (2005-2020) retrieved from Pubmed database and Google scholar search engine using "Cardiovascular Disease", "PEAR1", "Polymorphism", and "Platelet Aggregation" keywords...

The dorsal root ganglia (DRG) house the primary afferent neurons responsible for somatosensation, including pain. We previously identified Jedi-1 (PEAR1/MEGF12) as a phagocytic receptor expressed by satellite glia in the DRG involved in clearing apoptotic neurons during development. Here, we further investigated the function of this receptor in vivo using Jedi-1 null mice. In addition to satellite glia, we found Jedi-1 expression in perineurial glia and endothelial cells, but not in sensory neurons. We did not detect any morphological or functional changes in the glial cells or vasculature of Jedi-1 knockout mice...

BACKGROUND: Activation of the proliferation of pulmonary microvascular endothelial cells (PMVECs) is a key step in the recovery of the integrity of endothelial monolayer, which helps to alleviate acute lung injury (ALI). Platelet endothelial aggregation receptor-1 (PEAR1), expressed on endothelial cells, was reported to inhibit the proliferation of vascular endothelial cells and angiogenesis. However, little is known about its role and mechanism in vascular endothelial disorders in ALI...

BACKGROUND: Platelet-endothelial aggregation receptor 1 (PEAR-1) is a transmembrane receptor involved in platelet activation and megakaryopoiesis whose expression is driven by DNA methylation. PEAR1 variants were associated with differential platelet response to activation and cardiovascular outcomes. We aimed at investigating the link between PEAR1 methylation and platelet and leukocyte function markers in a family-based population. RESULTS: We measured PEAR1 methylation in 605 Moli-family participants with available blood counts, plasma P-selectin and C-reactive protein, whole blood platelet P-selectin, and platelet-leukocyte mixed conjugate measurements...

BACKGROUND: Hypertension (HTN) disproportionately affects African Americans (AAs), who respond better to thiazide diuretics than other antihypertensives. Variants of the APOL1 gene found in AAs are associated with a higher rate of kidney disease and play a complex role in cardiovascular disease. METHODS: AA subjects from four HTN trials (n = 961) (GERA1, GERA2, PEAR1, and PEAR2) were evaluated for blood pressure (BP) response based on APOL1 genotype after 4-9 weeks of monotherapy with thiazides, beta blockers, or candesartan...