title: 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.
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.
authors: UMR INSERM U 1122, IGE-PCV, Faculté de Pharmacie, Université de Lorraine, 30 Rue Lionnois, Nancy 54000, France. payman.shahabi@inserm.fr
authors: Payman
authors: P
authors: Shahabi
authors: Gérard
authors: G
authors: Siest
authors: Bernard
authors: B
authors: Herbeth
authors: Daniel
authors: D
authors: Lambert
authors: Christine
authors: C
authors: Masson
authors: Jean-Sébastien
authors: JS
authors: Hulot
authors: Sébastien
authors: S
authors: Bertil
authors: Pascale
authors: P
authors: Gaussem
authors: Sophie
authors: S
authors: Visvikis-Siest
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D019013:CD40 Antigens / Q000097:blood; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D056726:Genetic Association Studies; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D009961:Orosomucoid / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D019013:CD40 Antigens; D006242:Haptoglobins; D018836:Inflammation Mediators; D009961:Orosomucoid; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D002097:C-Reactive Protein; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
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