The rhCYP2C8 and rhCYP3A4 SNP variants included in our system and their metabolic activities compared with literature values
The CLints (which reflect the enzyme activity) of the SNP variants were compared with those of the prototypic enzymes (see Supplemental Table S1). The activities in parentheses are assumed activities based on the structural alterations or the metabolic ratio of probe substrate.
| P450 SNP Variants | Allele Number | Activitya | Literature Activity |
|---|---|---|---|
| CYP2C8.1 (prototype) | CYP2C8*1 | Normal | Normal |
| R139K | CYP2C8*3 | Normal | |
| CYP2C8.2 (I269F) | CYP2C8*2 | Decrease | Decreaseb |
| CYP2C8.3 (R139K, K399R) | CYP2C8*3 | Decrease | Decreaseb,c |
| K399R | CYP2C8*3 | Decrease | |
| CYP2C8.4 (I264M) | CYP2C8*4 | Decrease | Decreasec |
| CYP3A4.1 (prototype) | CYP3A4*1 | Normal | Normal |
| CYP3A4.18 (L293P) | CYP3A4*18 | Normal | Increased; normale,f,g |
| CYP3A4.7 (G56D) | CYP3A4*7 | Normal | Normalg,h |
| CYP3A4.9 (V170I) | CYP3A4*9 | Normal | Normalh |
| CYP3A4.3 (M445T) | CYP3A4*3 | Normal | Normald,f,h |
| CYP3A4.15 (R162Q) | CYP3A4*15 | Normal | (Normal)i |
| CYP3A4.14 (L15P) | CYP3A4*14 | Normal | (Normal)i |
| CYP3A4.4 (I118V) | CYP3A4*4 | Normal | (Decrease)j |
| CYP3A4.19 (P467S) | CYP3A4*19 | Normal | Normald,f |
| CYP3A4.2 (S222P) | CYP3A4*2 | Decrease | Decreaseg,k; normalk |
| CYP3A4.5 (P218R) | CYP3A4*5 | Decrease | (Decrease)j |
| CYP3A4.16 (T185S) | CYP3A4*16 | Decrease | (Normal)i; decreasee,g |
| CYP3A4.10 (D174H) | CYP3A4*10 | Decrease | Normalh |
| CYP3A4.12 (L373F) | CYP3A4*12 | Decrease | (Normal)i; decreaseh |
| CYP3A4.13 (P416L) | CYP3A4*13 | Decrease | No P450 holoproteinh |
| CYP3A4.11 (T363M) | CYP3A4*11 | Decrease | Decreasee,h |
| CYP3A4.8 (R130Q) | CYP3A4*8 | N.D. | No P450 holoproteinh |
| CYP3A4.17 (F189S) | CYP3A4*17 | N.D. | Decreased,f |
N.D., not detectable.
↵a The activities of the rhCYP2C8 and rhCYP3A4 enzymes were tested by using BOMCC and DBF, respectively, as substrates.
↵b Dai et al., 2001b;
↵c Bahadur et al., 2002;
↵d Dai et al., 2001a;
↵e Murayama et al., 2002;
↵f Lee et al., 2005;
↵g Miyazaki et al., 2008;
↵h Eiselt et al., 2001;
↵i Lamba et al., 2002;
↵j Hsieh et al., 2001;
↵k Sata et al., 2000.