Association of Genetic Variability in Selected Genes in Patients With Deep Vein Thrombosis and Platelet Hyperaggregability

Abstract

The aim of this study was to evaluate the genetic variability of the selected single nucleotide polymorphisms (SNPs) and examine the association between these SNPs and risk for deep vein thrombosis (DVT) in patients with sticky platelet syndrome (SPS). We examined 84 patients with SPS and history of DVT and 101 healthy individuals. We were interested in 2 SNPs within platelet endothelial aggregation receptor 1 (PEAR1) gene (rs12041331 and rs12566888), 2 SNPs within mkurine retrovirus integration site 1 gene (rs7940646 and rs1874445), 1 SNP within Janus kinase 2 gene (rs2230722), 1 SNP within FCER1G gene (rs3557), 1 SNP within pro-platelet basic protein (rs442155), 4 SNPs within alpha2A adrenergic receptor 2A (ADRA2A; rs1800545, rs4311994, rs11195419, and rs553668), and 1 SNP within sonic hedgehog gene (rs2363910). We identified 2 protective SNPs within PEAR1 gene and 1 risk SNP within ADRA2A gene (PEAR1: rs12041331 and rs12566888; ADRA2A: rs1800545). A haplotype analysis of 4 SNPs within ADRA2A gene identified a risk haplotype aagc ( P = .003). Moreover, we identified 1 protective haplotype within PEAR1 gene (AT, P = .004). Our results support the idea that genetic variability of PEAR1 and ADRA2A genes is associated with platelet hyperaggregability manifested as venous thromboembolism. The study also suggests a possible polygenic type of SPS heredity.

Influence of ABO Locus on PFA-100 Collagen-ADP Closure Time Is Not Totally Dependent on the Von Willebrand Factor. Results of a GWAS on GAIT-2 Project Phenotypes

“…These were located in different genes related to platelet functional receptors, regulators of cytoskeleton and signaling proteins. Among these genes, the following were described: MIR100HG , MME , PIP3-E , GLIS3 , LDHAL6A , ANKS1B , PIK3CG , MAGI1 , C8orf86 , FGFR1 , LPAR1 , CACNB2 , SLC39A12 , RPP25 , SCAMP5 , BMPR1A (revisited in Bunimov et al [19]), ANKRD26 [20], pannexin [21], ADRA2 [22] and the most relevant PEAR-1 [22,23,24]. Notably, none of these genetic variants was found in the ABO locus.…”

Genetic Variation in PEAR1, Cardiovascular Outcomes and Effects of Aspirin in a Healthy Elderly Population

“…Based on PEAR1 genotype, they observed significantly different ADP‐induced platelet aggregation (29.1, 25.4, and 22.9 for genotypes GG, GA, and AA, respectively, P = 0.0005) and detected differences in the 30‐day incidence of a composite cardiovascular phenotype consisting of cardiovascular death, nonfatal myocardial infarction, and ischemic stroke (HR = 2.78, 95% CI 1.13–6.82, P = 0.03). Positive associations with deep vein thrombosis in those with sticky platelet syndrome as well as coronary artery aneurysm in individuals with Kawasaki disease have also been shown by PEAR1 rs12041331 genotype 33,34 …”

“…Positive associations with deep vein thrombosis in those with sticky platelet syndrome as well as coronary artery aneurysm in individuals with Kawasaki disease have also been shown by PEAR1 rs12041331 genotype. 33,34 Further studies have suggested a genotype x aspirin interaction exists whereby aspirin-treated carriers of rs12041331 minor (A) allele have enhanced risk of experiencing a clinical event compared with carriers of the same allele who are not treated with aspirin. 29 Specifically, it was observed in patients with stable coronary artery disease of European descent that rs12041331 A-allele carriers treated with aspirin have significantly increased risk of myocardial infarction (odds ratio (OR) = 2.08, 95% CI 1.01-4.09, P = 0.048) compared with those who were not exposed to aspirin (OR = 0.25, 95% CI 0.03-2.03, P = 0.19).…”

Seasonal variations and the risk of venous thromboembolism: A narrative review article

“…26,27 Genetic variations may also be an important risk factor protecting or predisposing some people to VTE in winter. 28 It seems that the combination of inflammation, the amount of decreased temperature, genetic factors, age, and acute infections in winter and their interaction are important in predisposing some people to VTE during winter.…”