The value of using polymorphisms in anti-platelet therapy

doi:10.1007/s11515-017-1456-0

Front. Biol.

2017, Vol. 12

Issue (5) : 349-356 https://doi.org/10.1007/s11515-017-1456-0

REVIEW

The value of using polymorphisms in anti-platelet therapy

Habib Haybar, Zeinab Deris Zayeri(

)

Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

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Abstract

OBJECTIVES and BACKGROUNDS: Cardiovascular events occure as a result of various risk factors, such as uric acid (UA), inflammation, hormones and other materials that induce C- reactive protein (CRP) expression. These factors lead to complement activation, and endothelial damages. Damaged endothelial cells release heparan sulfate which inhibits tissue factor activity and von Willed brand factor (VWVF) and causes aggregation. Finally this cascade of events cause platelets aggregation and leads to heart ischemia and cardiovascular events.

DISCUSSION:Anti-platelet therapy is an interesting premise. Anti-platelet resistance patients and bleeding as a result of using ticagrelor and prasugrel should be considered in this treatment methods. Anti-platelet drugs such as clopidogrel are prescribed in cardiovascular events. Platelets have VWF receptors and P2Y12 receptors on their surface, and thus, targeting these receptors can be useful in treatment. The active metabolites of clopidogrel bind to P2Y12R and inhibit ADP binding; thus, clopidogrel inhibits aggregation by interfering in several events as a result of the inhibition of ADP attachment to P2Y12R of the platelet. However, the polymorphisms of P2Y12 and other genes mentioned in Table 1 showed treatment resistance in anti-platelet therapy, highlighting that these SNPs can be helpful in anti-platelet therapy.

CONCLUSION: The knowledge of these SNPs may decrease the number of unwanted effects that endanger patients with cardiovascular diseases and avoids ineffective anti-platelet therapy in several patients. Clopidogrel, ticagrelor, prasugrel, and aspirin and CYP2C19 and their SNPs are very important subjects in anti-platelet therapy. To present the importance of using pharmacogenetics in anti-platelet therapy, we discuss here the association between these drugs and the SNPs for therapeutic resistance.

Keywords cardiovascular events clopidogrel CYP2C19 polymorphisms anti-platelet drugs

Corresponding Author(s): Zeinab Deris Zayeri

Online First Date: 02 November 2017 Issue Date: 20 November 2017

Cite this article:

Habib Haybar,Zeinab Deris Zayeri. The value of using polymorphisms in anti-platelet therapy[J]. Front. Biol., 2017, 12(5): 349-356.

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https://academic.hep.com.cn/fib/EN/10.1007/s11515-017-1456-0
https://academic.hep.com.cn/fib/EN/Y2017/V12/I5/349

Fig.1 Uric acid, inflammation, hormones, and other stimuli damage endothelial cells. VWF increased on the damaged endothelial surface, but heparan sulfate decreased. These changes in the epithelial surface cause platelet adherence, aggregation, and ultimately plaque formation. Anti-platelet drugs disrupt the plaques; these drugs produce metabolites that inhibit platelet activation by attaching to P2Y12R. Clopidogrel is a pro-drug that reacts with CYP450 to be transformed to its active metabolite. The metabolites then bind to P2Y12R and inhibit G-protein (GP), which leads to PI3K inhibition and decreased GP expression on the platelet surface. GP mediates fibrinogen binding to platelets and causes aggregation, adherence, and thrombus formation. Abbreviations: UA, uric acid; VWF, Von Willebrand Factor; ADP, Adenosine di-phosphate; PI3K, phosphoinositide3-kinase; CES, primarily carboxylesterase 1; GP, Glycoprotein; CYP450, cytochrome P450 enzymes.

Tab.1 Notable SNPs in anti-platelet therapy

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