Variants in COX-2 , PTGIS , and TBXAS1 Are Associated with Carotid Artery or Intracranial Arterial Stenosis and Neurologic Deterioration in Ischemic Stroke Patients

Yi, Xingyang; Ming, Bing; Wang, Chun; Chen, Hong; Ma, Chun

doi:10.1016/j.jstrokecerebrovasdis.2016.12.032

Cited by 14 publications

(22 citation statements)

References 33 publications

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“…TXA2, TXA2R, platelet membranes receptors, and glycoprotein IIIa are all very crucial for platelet activation [11–13]. Our previous studies and some other studies have shown that polymorphisms of TXA2R and TXAS1 genes are associated with platelet activation, and independently associated with the risk of carotid plaque vulnerability, carotid or intracranial arterial stenosis and IS [7, 15, 28–30]. In healthy subjects, platelet activation was associated with a haplotype of the P2Y12 gene [31].…”

Section: Discussionmentioning

confidence: 99%

“…Venous blood (3 mL) was drawn from an arm vein into a sterile tube containing ethylenediaminetetraacetic acid. Genomic DNA was extracted from peripheral blood using a modified phenol/chloroform method and purified using the UNIQ-10 kit (Sangon Biotech Co., Ltd. Shanghai, China) [7, 8]. As the previous study described, adopting matrix-assisted laser desorption ionization through time-of-flight mass spectrometry to detect genotypes of the 11 variants [7, 8, 15, 16].…”

Section: Methodsmentioning

confidence: 99%

“…Variants in inflammation and endothelial functions genes have been reported to play roles in atherosclerosis pathogenesis in the Dominican population [6]. In 2016, our previous studies illustrated the variants in Cytochrome P450 genes and eicosanoid genes were independently associated with carotid stenosis [7, 8]. However, until now the genetic etiology of carotid stenosis has not been sufficiently recognized.…”

Section: Introductionmentioning

confidence: 99%

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The TXA2R rs1131882, P2Y1 rs1371097 and GPIIIa rs2317676 three-loci interactions may increase the risk of carotid stenosis in patients with ischemic stroke

Lin

Zhou

et al. 2019

BMC Neurol

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BackgroundThe genetic risk factors for carotid stenosis are not fully understood. The aim of this study is to investigate the relationship between variants in platelet activation-relevant genes and carotid stenosis in patients with ischemic stroke (IS).MethodsEleven variants of platelet activation-relevant genes, aggregates of platelet-leukocyte, and platelet aggregation were examined in 236 IS patients with carotid stenosis and 378 patients without carotid stenosis. High-resolution B-mode ultrasound was used to assess carotid stenosis. Generalized multifactor dimensionality reduction (GMDR) methods were applied in analyzing gene-gene interactions to determine whether there was any interactive role of assessed variants in affecting risk of carotid stenosis.ResultsPlatelet aggregation and aggregates of platelet-leukocyte showed higher value in patients with carotid stenosis, compared with patients without carotid stenosis. Excluding potential disturbance variables, these 11 variants were not associated with carotid stenosis. However, according to the GMDR analysis, gene-gene interactions among TXA2R rs1131882, P2Y1 rs1371097 and GPIIIa rs2317676 had a synergistic influence on carotid stenosis. The high-risk interactions between the three variants showed a relationship with higher platelet activation, and have independent associations with risk of carotid stenosis (OR = 2.72, 95% CI: 1.28–7.82, P = 0.001).ConclusionThe interactions among rs1131882, rs1371097 and rs2317676 perhaps increase the risk of symptomatic carotid stenosis, and maybe a potential marker for carotid stenosis. In this study, the combinatorial analysis made good use in elucidating complex risk factors in the heredity of carotid stenosis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The TXA2R rs1131882, P2Y1 rs1371097 and GPIIIa rs2317676 three-loci interactions may increase the risk of carotid stenosis in patients with ischemic stroke

Lin

Zhou

et al. 2019

BMC Neurol

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“…Up to date, the association of TBXAS1 variation with cardiovascular disease and ischemic stroke has not been well addressed. Our recent study showed that TXAS1 rs41708 polymorphisms were independent risk factors for symptomatic carotid artery or intracranial arterial stenosis [42]. Variants of TXA2R led to increased ligand binding-induced intracellular calcium influx and fibrinogen-integrin conjugation, may affect platelet function and the risk of developing cerebral infarction [14,21,22].…”

Section: Discussionmentioning

confidence: 99%

Genetic variants of PTGS2, TXA2R and TXAS1 are associated with carotid plaque vulnerability, platelet activation and TXA2 levels in ischemic stroke patients

Lin

Luo

et al. 2017

PLoS ONE

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Eicosanoids may play a role in ischemic stroke. However, the associations of variants in cyclooxygenase (COX) pathway genes and interaction among these variants with carotid plaque vulnerability are not fully understood. In present study, twelve variants in COX pathway genes were examined using matrix-assisted laser desorption ionization time-of-flight mass spectrometry method in 396 patients with ischemic stroke and 291 controls. Platelet aggregation, platelet-leukocyte aggregates, and urine 11-dehydrothromboxane B2 (11-dTxB2) were also measured. According to the results of carotid high-resolution B-mode ultrasound, the patients were stratified into the following groups [i.e., non-carotid plaque and carotid plaque. The carotid plaque was further classified into subgroups of echolucent plaque (ELP) and echogenic plaque (EGP)]. Additionally, gene-gene interactions were analyzed to assess whether there was any interactive role for assessed variants in affecting carotid plaque vulnerability, platelet activation and 11-dTxB2 levels. There were no significant differences in the frequencies of genotypes of the twelve variants between patients and controls. Among 396 patients, 294 cases (74.2%) had carotid plaques (106 had ELP, 188 had EGP). Frequency of PTGS2 rs20417CC, TXAS1 rs2267679TT, TXAS1 rs41708TT, PTGIS rs5602CC, and TXA2R rs1131882TT genotype was significantly higher in patients with plaque compared with patients without plaque, or in patients with ELP compared with patients with EGP. 11-dTxB2 levels, platelet aggregation and platelet-leukocyte aggregates were significantly higher in patients with ELP compared with patients without plaque or with EGP. Multivariate logistic regression analysis revealed that PTGS2 rs20417CC, TXA2R rs1131882TT, and high-risk interaction among variants in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were independently associated with the risk of ELP after adjusting for confounding variables. The variants in COX pathway genes and the high-risk interactions among variants in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were associated with high 11-dTxB2 and platelet activation, and independently associated with the risk of carotid plaque vulnerability. These variants might be potential markers for plaque instability.

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“…10,11 The disorder has also been associated with vascular atherosclerosis, 12 which is one of the most important mechanisms of ischemic stroke, and which increases the risk of migraine. Carotid artery stenosis is an important change in patients with ischemic stroke, 13,14 and carotid intima-media thickness (IMT) is often assessed to monitor the pathological condition of atherosclerosis in clinical practice. 15 Some studies have also assessed this index in patients with migraine 16,17 and showed that migraine patients had greater carotid IMT than controls.…”

Section: Introductionmentioning

confidence: 99%

Ultrasonic assessment of carotid intima-media thickness in migraine: a meta-analysis

2019

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Objective Migraine is believed to be a risk factor for cerebrovascular diseases, and previous studies have indicated an association between migraine and cerebral atherosclerosis. Carotid artery intima-media thickness (IMT) is considered to be a biomarker of atherosclerosis pathology. This study aimed to investigate the relationship between carotid IMT and migraine by conducting a meta-analysis. Methods We searched Web of Science, PubMed, and the Cochrane Library for eligible studies assessing carotid IMT in patients with migraine and controls. Data were extracted independently by two reviewers and analyzed using Review Manager 5.3 software. Results The meta-analysis included seven articles with 555 subjects (279 migraine patients, 276 controls). Carotid IMT was significantly greater in patients with migraine compared with controls. However, there were no significant differences in IMT between patients with migraine with aura (MA) and controls, migraine without aura (MO) and controls, and patients with MA and MO. Conclusion Patients with migraine have greater carotid IMT than individuals without migraine, suggesting an association between atherosclerosis and migraine. However, further studies with more samples are needed to confirm this finding.

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Variants in COX-2 , PTGIS , and TBXAS1 Are Associated with Carotid Artery or Intracranial Arterial Stenosis and Neurologic Deterioration in Ischemic Stroke Patients

Cited by 14 publications

References 33 publications

The TXA2R rs1131882, P2Y1 rs1371097 and GPIIIa rs2317676 three-loci interactions may increase the risk of carotid stenosis in patients with ischemic stroke

The TXA2R rs1131882, P2Y1 rs1371097 and GPIIIa rs2317676 three-loci interactions may increase the risk of carotid stenosis in patients with ischemic stroke

Genetic variants of PTGS2, TXA2R and TXAS1 are associated with carotid plaque vulnerability, platelet activation and TXA2 levels in ischemic stroke patients

Ultrasonic assessment of carotid intima-media thickness in migraine: a meta-analysis

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