Interactions among variants in  TXA2R, P2Y12  and  GPIIIa  are associated with carotid plaque vulnerability in Chinese population

Xingyang Yi; Jing Lin; Hua Luo; Ju Zhou; Qiang Zhou; Yanfen Wang; Chun Wang

doi:10.18632/oncotarget.24801

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Research Papers:

Interactions among variants in TXA2R, P2Y12 and GPIIIa are associated with carotid plaque vulnerability in Chinese population

Xingyang Yi, Jing Lin _, Hua Luo, Ju Zhou, Qiang Zhou, Yanfen Wang and Chun Wang

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Oncotarget. 2018; 9:17597-17607. https://doi.org/10.18632/oncotarget.24801

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Abstract

Xingyang Yi1, Jing Lin2,*, Hua Luo3,*, Ju Zhou1, Qiang Zhou2, Yanfen Wang1 and Chun Wang1

1Department of Neurology, The People’s Hospital of Deyang City, Deyang 618000, Sichuan, China

2Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, Zhejiang, China

3Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China

*These authors contributed equally to this work

Correspondence to:

Jing Lin, email: [email protected], [email protected]

Hua Luo, email: [email protected]

Keywords: ischemic stroke; carotid atherosclerosis; carotid plaque vulnerability; genetic polymorphism; platelet activation

Received: December 04, 2017 Accepted: March 12, 2018 Published: April 03, 2018

ABSTRACT

Purpose: The 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.

Results: There 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.

Methods: Eleven 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.

Conclusions: 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.

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Research Papers:

Interactions among variants in TXA2R, P2Y12 and GPIIIa are associated with carotid plaque vulnerability in Chinese population

Abstract