CYP2C9 Allelic Variants

Pharmacogenetics in Potential Herb-Drug Interactions Effects of Ginseng on CYP3A4 and CYP2C9 Allelic Variants... 

Xie HG, Prasad HC, Kim RB, Stein CM (2002) CYP2C9 allelic variants ethnic distribution and functional significance. Adv. Drug Delivery Review 54 1257-1270 Yasar U, Dahl ML, Christensen M, Eliasson E (2002) Intraindividual variability in urinary losartan oxidation ratio, an in vivo marker of CYP2C9 activity. Br J Clin Pharmacol 54 183-185... 

Palacio L, et al. Pharmacogenetic Impact of VKORC1 and CYP2C9 Allelic Variants on warfarin dose requirements in a Hispanic population isolate. Clin Appl Thromb Hemost. 2009 16 83-90. 

Niinuma Y, Saito T, Takahashi M, Tsukada C, Ito M, Hirasawa N, Hiratsuka M (2014) Functional characterization of 32 CYP2C9 allelic variants. Pharma-cogenomics J 14 107-114... 

Rettie, A. E. etal. (1994). Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics, 4, 39 42. 

CYP2C9 Multiple allelic variants of CYP2C9 may account for the occurrence of poor metabolizers and increased efficacy of warfarin (84)... 

In terms of the impact of polymorphisms, our results demonstrated that genetic mutations did not lead to differences in the inhibition of CYP2C9 or its allelic variants. This suggests that genetic background may not be involved in the predisposition of herb-drug interactions for ginseng with this enzyme. 

The third relatively well-characterized genetic polymorphism is that of CYP2C9. Two well-characterized variants of this enzyme exist, each with amino acid mutations that result in altered metabolism. The CYP2C9 2 allele encodes an Argl44Cys mutation, exhibiting impaired functional interactions with P450 reductase. The other allelic variant,... 

Figure 1 The INR values and warfarin doses of a patient with CYP2C9 3 allelic variant requiring over 1 year to maintain a therapeutic INR.

Sullivan-Klose TH, Ghanayem BI, Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM, et al. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 1996 6 341-9. 

The CYP2C9 5 variant has only been observed in African Americans, such that approximately 3% of this population carries the CYP2C9 5 allele. In vitro intrinsic clearances for CYP2C9 5, calculated as the ratio of Vnjax/ ranged from 8 to 18%of CYP2C9 1 values in the initial report (44). The CYP2C9 6 variant results in a frameshift mutation. To date, it has only been observed in one Caucasian patient (R. S. Kidd, personal communication). 

Borgiani P, Ciccacci C, Forte V, etal. Allelic variants in the CYP2C9 and VKORCl loci and interindividual variability in the anticoagulant dose effect of warfarin in Italians. Pharmacogenomics 2007 8(ll) 1545-50. 

An example of genetic variation within the CYP family would be with the CYP2C9 variants (CYP2C9 , 2, 3). The allelic variants differ in their affinity (K ) and/or intrinsic clearance for CYP2C9 substrates... 

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