Abstract

PurposeThe associations between variants in platelet activation-relevant genes and carotid plaque vulnerability are not fully understood. The aim of the present study was to investigate the associations of the variants in platelet activation-relevant genes and interactions among these variants with carotid plaque vulnerability.ResultsThere were no significant differences in the frequencies of genotypes of the 11 variants between patients and controls. Among 396 patients, 102 patients had not carotid plaque, 106 had VP, and 188 had SP. The 11 variants were not independently associated with risk of carotid plaque vulnerability after adjusting for potential confounding variables. However, the GMDR analysis showed that there were synergistic effects of gene-gene interactions among TXA2Rr s1131882, GPIIIa rs2317676 and P2Y12 rs16863323 on carotid plaque vulnerability. The high-risk interactions among the three variants were associated with high platelet activation, and independently associated with the risk of carotid plaque vulnerability.MethodsEleven variants in platelet activation-relevant genes were examined using mass spectrometry methods in 396 ischemic stroke patients and 291controls. Platelet-leukocyte aggregates and platelet aggregation were also measured. Carotid plaques were assessed by B-mode ultrasound. According to the results of ultrasound, the patients were stratified into three groups: non-plaque group, vulnerable plaque (VP) group and stable plaque (SP) group. Furthermore, gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods.ConclusionsThe rs1131882, rs2317676, and rs16863323 three-loci interactions may confer a higher risk of carotid plaque vulnerability, and might be potential markers for plaque instability.

Highlights

  • Stroke is one of leading causes of mortality and disability in China [1, 2]

  • The rs1131882, rs2317676, and rs16863323 three-loci interactions may confer a higher risk of carotid plaque vulnerability, and might be potential markers for plaque instability

  • Diabetes mellitus and hypertension were more frequent in patients than controls (Table1)

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Summary

Introduction

Stroke is one of leading causes of mortality and disability in China [1, 2]. Carotid atherosclerosis is a major risk factor for ischemic stroke (IS). Carotid plaque rupture or vulnerable lesions may obstruct the blood vessels of the brain by atherothrombosis or emboli [3, 4].The degree of carotid stenosis alone may not be sufficient to evaluate the risk of stroke [5]. The cholucent plaque or ulcerative plaque in carotid may play a more important role in the occurrence of cerebrovascular events than carotid stenosis [5, 6]. Identifying novel etiologies of carotid www.oncotarget.com plaque vulnerability, including the genetic etiology is very important for preventing stroke [7]. Up to date, such a genetic etiology has not been fully understood

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