VASP phosphorylation and genetic polymorphism for clopidogrel resistance in Chinese patients with non-cardioembolic ischemic stroke

Zhang, Shijun; Lai, Xinqiang; Li, Wenxian; Jing, Zhen; Xiong, Zhilin; Xu, Anding; Ruan, Yiwen

doi:10.1016/j.thromres.2014.10.001

Cited by 22 publications

(23 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11,20 Moreover, 10 of 11 (90.9%) studies that recruited subjects within 1 week after the index stroke demonstrated significant associations with CYP2C19 variants. [8][9][10][11][12][16][17][18][19][20] In contrast, none of 3 studies that recruited subjects within >2 weeks of the index stroke showed significant relationships. In a cardiological study, Arima et al…”

Section: Discussionmentioning

confidence: 99%

“…7 To our knowledge, all related studies have consistently showed a relationship between CYP2C19 variants and platelet reactivity. [8][9][10][11][12] However, several studies have failed to show a connection between the genetic variants and the rate of cardiovascular events. [13][14][15] To address these inconsistent results, we hypothesized that differences in the elapsed time from stroke onset might affect the relationship between the genetic variants and cardiovascular events because most studies enrolled stroke patients in the acute phase (within 1 week of the index of stroke).…”

Section: Vasodilator-stimulated Phosphoprotein (Vasp) Index Analysismentioning

confidence: 99%

“…[13][14][15] To address these inconsistent results, we hypothesized that differences in the elapsed time from stroke onset might affect the relationship between the genetic variants and cardiovascular events because most studies enrolled stroke patients in the acute phase (within 1 week of the index of stroke). [8][9][10][11][12][15][16][17][18][19][20] We therefore prospectively investigated whether CYP2C19 variants affected cardiovascular events during 2 years of follow-up in the chronic phase of stroke.…”

Section: Vasodilator-stimulated Phosphoprotein (Vasp) Index Analysismentioning

confidence: 99%

See 2 more Smart Citations

Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

Yamagami

Ihara

Miyata

et al. 2019

Circ J

View full text Add to dashboard Cite

Background: CYP2C19 variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect of CYP2C19 variants on clinical outcomes in the chronic phase. Methods and Results: In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according to CYP2C19 genotype: extensive metabolizer (EM: *1/*1), intermediate metabolizer (IM: *1/*2 or *1/*3), and poor metabolizer (PM: *2/*2, *2/*3, or *3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups. Conclusions: Despite associations between CYP2C19 variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups of CYP2C19 variants.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Vasodilator-stimulated Phosphoprotein (Vasp) Index Analysismentioning

confidence: 99%

Section: Vasodilator-stimulated Phosphoprotein (Vasp) Index Analysismentioning

confidence: 99%

See 1 more Smart Citation

Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

Yamagami

Ihara

Miyata

et al. 2019

Circ J

View full text Add to dashboard Cite

show abstract

“…More than half (53) of the top 100 genes were found to be related to phosphoprotein, which is significantly enriched compared with normal backgrounds (p < 0.002). Although previous studies have discovered that some kinds of phosphor-proteins (such as VASP) are involved with brain-blood barrier damage or neural protections following stroke and other cerebral diseases 60 , the pervasive correlation between the stroke marker genes and phosphoproteins suggests that more investigations are merited regarding the role of phosphoproteins in stroke onset and development.…”

Section: Resultsmentioning

confidence: 99%

Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study

Wang

Cai

2016

Sci Rep

View full text Add to dashboard Cite

Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages. An important inquiry is how well the findings of animal models can be replicated in human cases. Here, a method is proposed based on PageRank scores of miRNA-mRNA interaction network to select ischemic stroke biomarkers derived from rat brain samples, and biomarkers are validated with two human peripheral blood gene expression datasets. Hierarchical clustering results revealed that the achieved biomarkers clearly separate the blood gene expression of stroke patients and healthy people. Literature searches and functional analyses further validated the biological significance of these biomarkers. Compared to the traditional methods, such as differential expression, the proposed approach is more stable and accurate in detecting cross-species biomarkers with biological relevance, thereby suggesting an efficient approach of re-using gene biomarkers obtained from animal-model studies for human diseases.

show abstract

“…Various techniques have been used to genotype clopidogrel resistance associated SNP alleles. Sanger sequencing is considered as the gold standard 9 , 10 . It has a high cost and requires at least one day after PCR to obtain the result.…”

Section: Introductionmentioning

confidence: 99%

A Novel Multiplex HRM Assay to Detect Clopidogrel Resistance

Zhang

You

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Clopidogrel is an antiplatelet medicine used to prevent blood clots in patients who have had a heart attack, stroke, or other symptoms. Variability in the clinical response to clopidogrel treatment has been attributed to genetic factors. In particular, five SNPs of rs4244285, rs4986893, rs12248560, rs662 and rs1045642 have been associated with resistance to clopidogrel therapy in Chinese population. This work involves the development of a multiplex high-resolution melting (HRM) assay to genotype all five of these loci in 2 tubes. Amplicons corresponding to distinct SNPs in a common tube were designed with the aid of uMelt prediction software to have different melting temperatures Tm by addition of a GC-rich tail to the 5′ end of the certain primers. Two kinds of commercial methods, Digital Fluorescence Molecular Hybridization (DFMH) and Sanger sequencing, were used as a control. Three hundred sixteen DFMH pretested samples from consecutive acute coronary syndrome patients were used for a blinded study of multiplex HRM. The sensitivity of HRM was 100% and the specificity was 99.93% reflecting detection of variants other than the known resistance SNPs. Multiplex HRM is an effective closed-tube, highly accurate, fast, and inexpensive method for genotyping the 5 clopidogrel resistance associated SNPs.

show abstract

VASP phosphorylation and genetic polymorphism for clopidogrel resistance in Chinese patients with non-cardioembolic ischemic stroke

Cited by 22 publications

References 26 publications

Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study

A Novel Multiplex HRM Assay to Detect Clopidogrel Resistance

Contact Info

Product

Resources

About