Variants in clopidogrel-relevant genes and early neurological deterioration in ischemic stroke patients receiving clopidogrel

Yi, Xingyang; Zhou, Qiang; Zhang, Yongyin; Zhou, Ju; Lin, Jing

doi:10.1186/s12883-020-01703-6

Cited by 6 publications

(3 citation statements)

References 36 publications

(71 reference statements)

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“…Furthermore, the synergistic effect of genes interactions may contribute not only to platelet activity but also to stroke prognosis. Yi et al [ 37 ] showed that carriers of high-risk interactive genotypes not only exhibit a significantly lower platetet inhibition, but are also at a higher risk of early neurological deterioration than noncarriers (hazard ratio (HR) = 2.82; p = 0.003). The molecular mechanisms responsible for the above characteristics still remain unclear.…”

Section: Factors Influencing Clopidogrel Resistancementioning

confidence: 99%

The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review

Wiśniewski

Filipska

2020

IJMS

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Clopidogrel is increasingly being used for the secondary prevention of ischemic stroke according to the updated guidelines on acute stroke management. Failure to achieve a drug response is referred to as clopidogrel resistance. Similarly, a higher activation of platelets during clopidogrel therapy—high on-treatment platelet reactivity—is equivalent to a reduced effectiveness of a therapy. Clopidogrel resistance is considered to be a common and multifactorial phenomenon that significantly limits the efficacy of antiplatelet agents. The aim of the current study is to review the latest literature data to identify the prevalance and predictors of clopidogrel high on-treatment platelet reactivity among stroke subjects and to establish the potential impact on clinical outcomes and prognosis. Clinical databases were searched by two independent researchers to select relevant papers on the topic, including all types of articles. Several important predictors contributing to clopidogrel resistance were identified, including genetic polymorphisms, the concomitant use of other drugs, or vascular risk factors, in particular nonsmoking and diabetes. Clopidogrel high on-treatment platelet reactivity has a negative impact on the clinical course of stroke, worsens the early- and long-term prognoses, and increases the risk of recurrent vascular events. Platelet function testing should be considered in selected stroke individuals, especially those predisposed to clopidogrel resistance, for whom an improvement in the efficacy of antiplatelet therapy is essential. This particular group may become the greatest beneficiaries of the modification of existing therapy based on platelet function monitoring.

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Section: Factors Influencing Clopidogrel Resistancementioning

confidence: 99%

The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review

Wiśniewski

Filipska

2020

IJMS

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“… 38 The rs6809699 SNP and rs16863323 SNP in the LD block that also contains the rs3732759 SNP of the P2RY12 gene have been reported to be associated with intravenous immunoglobulin resistance in Kawasaki disease patients 39 and early neurological deterioration in acute ischemic stroke. 40 However, no previous studies have shown that the rs3732759 SNP of the P2RY12 gene and SNPs in the same LD block are associated with pain. Individuals who are homozygous for the major allele of the rs3732759 SNP may have higher P2RY12 expression, which may be more active in microglia and predispose these individuals to neuropathic pain, including PTP.…”

Section: Discussionmentioning

confidence: 99%

Single-nucleotide polymorphisms of the SLC17A9 and P2RY12 genes are significantly associated with phantom tooth pain

et al. 2022

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Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. We focused on solute carrier family 17 member 9 (SLC17A9)/vesicular nucleotide transporter (VNUT) and purinergic receptor P2Y12 (P2RY12), both of which have been associated with neuropathic pain and pain transduction signaling in the trigeminal ganglion in rodents. We sought to corroborate these associations in humans. We investigated gene polymorphisms that contribute to PTP. We statistically examined the association between genetic polymorphisms and PTP vulnerability in 150 patients with orofacial pain, including PTP, and 500 healthy subjects. We found that the rs735055 polymorphism of the SLC17A9 gene and rs3732759 polymorphism of the P2RY12 gene were associated with the development of PTP. Carriers of the minor allele of rs735055 and individuals who were homozygous for the major allele of rs3732759 had a higher rate of PTP. Carriers of the minor allele of rs735055 reportedly had high SLC17A9 mRNA expression in the spinal cord, which may increase the storage and release of adenosine triphosphate. Individuals who were homozygous for the major allele of rs3732759 may have higher P2RY12 expression that is more active in microglia. Therefore, these carriers may be more susceptible to PTP. These results suggest that specific genetic polymorphisms of the SLC17A9 and P2RY12 genes are involved in PTP. This is the first report on genes that are associated with PTP in humans.

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“…The current methods for identifying high-risk individuals depend largely on the assessment of the clinical and neuroimaging features present at the time of onset. In recent years, researchers have focused more on END in ischemic stroke (8)(9)(10). It was reported that the maximum body temperature and fever burden within 24 h after endovascular thrombectomy were independent predictors of END in ischemic stroke patients with large vessel occlusion (11).…”

Section: Introductionmentioning

confidence: 99%

Fever burden within 24 h after hematoma evacuation predicts early neurological deterioration in patients with intracerebral hemorrhage: a retrospective analysis

Xiong

et al. 2023

Front. Neurol.

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BackgroundEarly neurological deterioration after hematoma evacuation is closely associated with a poor prognosis in patients with intracerebral hemorrhage. However, the relationship between body temperature after hematoma evacuation and early neurological deterioration remains unclear. Therefore, this study aims to explore the possible relationship between body temperature and early neurological deterioration in patients with intracerebral hemorrhage after hematoma evacuation.MethodsWe retrospectively collected data from patients with cerebral hemorrhage at our institute between January 2017 and April 2022. The Student’s t-test, Mann–Whitney U-test, and χ2 Test and Fisher’s exact test were used to analyze the clinical baseline data. A univariate logistic regression model was used to evaluate the association between the body temperature indices and early neurological deterioration. The predictive power was assessed using the area under the Receiver Operating Characteristic (ROC) curve. The secondary outcome was a poor functional outcome.ResultsAmong 2,726 patients with intracerebral hemorrhage, 308 who underwent hematoma evacuation were included in the present analysis. A total of 82 patients (22.6%) developed early neurological deterioration. Univariate analysis showed that sex (p = 0.041); body temperature at 6 h (p = 0.005), 12 h (p = 0.01), and 24 h (p = 0.008) after surgery; duration of fever (p = 0.008); and fever burden (p < 0.001) were associated with early neurological deterioration. Multivariate logistic regression showed that fever burden was independently associated with early neurological deterioration (OR = 1.055 per °C × hour, 95%CI 1.008–1.103, p = 0.020). ROC showed that fever burden (AUC = 0.590; 95%CI: 0.514–0.666) could predict the occurrence of early neurological deterioration.ConclusionFever burden is associated with early neurological deterioration in intracerebral hemorrhage patients undergoing hematoma evacuation. Our findings add to previous evidence on the relationship between the fever burden and the occurrence of early neurological deterioration in patients with intracerebral hemorrhage. Future studies with larger sample sizes are required to confirm these findings.

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Variants in clopidogrel-relevant genes and early neurological deterioration in ischemic stroke patients receiving clopidogrel

Cited by 6 publications

References 36 publications

The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review

The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review

Single-nucleotide polymorphisms of the SLC17A9 and P2RY12 genes are significantly associated with phantom tooth pain

Fever burden within 24 h after hematoma evacuation predicts early neurological deterioration in patients with intracerebral hemorrhage: a retrospective analysis

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