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Cytochromes P450 et Tonus Vasculaire

Abstract : Several markers of inflammation are predictors of cardiovascular events. Among inflammatory factors, Interleukines (IL)- 6, Tumor Necrosis Factor-[alpha] (TNF-[alpha]) and C-Reactive Protein. These inflammatory markers notably interleukine regulate drug metabolizing enzymes : the cytochrome P450. These enzymes are also involved in metabolism of endogenous compounds such as arachidonic acid to produce epoxyeicosanoid acids (EETs), which play an important role in vascular tone and inflammation. This study described in a healthy population the possible relationship between inflammatory markers and polymorphism of CYP2C19*2 characterized by two SNPs : 681G>A and 990C>T. In our population, the frequencies of the alleles 681A and 990T were 17.8% and 18.4% respectively. We have demonstrated that plasma levels of inflammatory factors notably interleukine-6 were increased in the less frequent alleles carriers. The nonfonctional enzyme product of CYP2C19*2 mutated gene will not produce this metabolite, deprivating the body of its anti-inflammatory properties. Moreover, we observed an increase in serum concentration of triglycerides in the individuals carrying the CYP2C19*2 allele. Then we could suggest that individuals with CYP2C19*2 mutation are poor metabolizers for arachidonic acid and the excess of n-6 fatty acid correlate with the risk for inflammation, indicated by the level ofIL-6. The correlation between inflammatory marker and CYP2C19*2 polymorphism suggest that CYP2C19 could be considered as a new candidate gene in the cardiovascular diseases.
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Céline Bertrand-Thiébault. Cytochromes P450 et Tonus Vasculaire. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2004. Français. ⟨NNT : 2004NAN10260⟩. ⟨tel-01746962⟩



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