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Int. J. Mol. Sci. 2013, 14(8), 16402-16413; doi:10.3390/ijms140816402

Influence of Genetic Variations on Levels of Inflammatory Markers of Healthy Subjects at Baseline and One Week after Clopidogrel Therapy; Results of a Preliminary Study

1
UMR INSERM U 1122, IGE-PCV, Faculté de Pharmacie, Université de Lorraine, 30 Rue Lionnois, Nancy 54000, France
2
INSERM UMR S956, Université Pierre et Marie Curie, Paris 75005, France
3
AP-HP, Hôpital Européen Georges Pompidou, Paris 75908, France
4
Sorbonne Paris Cité, Université Paris Descartes, Paris 75270, France
5
INSERM UMR S765, Faculté de Pharmacie, Université Paris V, Paris 75006, France
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 7 June 2013 / Revised: 29 July 2013 / Accepted: 30 July 2013 / Published: 8 August 2013
(This article belongs to the Special Issue Xenobiotic Metabolism)
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Abstract

We aimed to assess the association between the most common polymorphisms of cytochrome P450 (CYP) epoxygenases on the plasma levels of inflammatory markers in a population of healthy subjects. We also sought to determine whether CYP2C19*2 polymorphism is associated with the anti-inflammatory response to clopidogrel. In a population of 49 healthy young males, the baseline plasma levels of inflammatory markers including C-reactive protein, haptoglobin, orosomucoid acid, CD-40 were compared in carriers vs. non-carriers of the most frequent CYP epoxygenase polymorphisms: CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C8*2 and CYP2J2*7. Also, the variation of inflammatory markers from baseline to 7 days after administration of 75 mg per day of clopidogrel were compared in carriers vs. non-carriers of CYP2C19* allele and also in responders vs. hypo-responders to clopidogrel, determined by platelet reactivity tests. There was no significant association between epoxygenase polymorphisms and the baseline levels of inflammatory markers. Likewise, CYP2C19* allele was not associated with anti-inflammatory response to clopidogrel. Our findings did not support the notion that the genetic variations of CYP epoxygenases are associated with the level of inflammatory markers. Moreover, our results did not support the hypothesis that CYP2C19*2 polymorphism is associated with the variability in response to the anti-inflammatory properties of clopidogrel. View Full-Text
Keywords: inflammation; cytochrome P450; polymorphism; epoxyeicosatrienoic acids; clopidogrel; C-reactive protein; haptoglobin inflammation; cytochrome P450; polymorphism; epoxyeicosatrienoic acids; clopidogrel; C-reactive protein; haptoglobin
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Shahabi, P.; Siest, G.; Herbeth, B.; Lambert, D.; Masson, C.; Hulot, J.-S.; Bertil, S.; Gaussem, P.; Visvikis-Siest, S. Influence of Genetic Variations on Levels of Inflammatory Markers of Healthy Subjects at Baseline and One Week after Clopidogrel Therapy; Results of a Preliminary Study. Int. J. Mol. Sci. 2013, 14, 16402-16413.

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