TABLE 1.
Studies that have investigated single nucleotide polymorphisms associated carbamazepine metabolism
| Study reference | Population | No. of subjects | SNP ID | Gene | Nucleotide change/allele | Effect of polymorphism |
|---|---|---|---|---|---|---|
| Ma et al. 2015 24 | Chinese | 166 | rs2242480 | CYP3A4 | *1G | NS |
| rs776746 | CYP3A5 | *3 | NS | |||
| rs1051740 | EPHX1 | c.337 T > C | Higher CBZ maintenance dose, lower CBZ natural logarithmic concentration–dose ratio and higher CBZE concentration | |||
| rs7439366 | UGT2B7 | c.802 T > C | Higher CBZ maintenance dose if also a carrier of ABCC2 c.1249G > A | |||
| rs3740066 | ABCC2 | c.3972C > T |
Higher CBZ maintenance dose and higher CBZE concentration Higher CBZ maintenance dose if also a carrier of UGT2B7 c.802 T > C |
|||
| rs2273697 | c.1249G > A | |||||
| Wang et al. 2015 25 | Chinese | 88 | rs4646440 | CYP3A4 | c.1023 + 608C > T | NS |
| rs2242480 | *1G | NS | ||||
| rs15524 | CYP3A5 | *1D |
Higher dose adjusted CBZ and CBZE concentration in subjects on concomitant PHT/PB Higher dose adjusted CBZ and CBZE concentration in subjects on concomitant PHT/PB |
|||
| *3 | ||||||
| rs776746 | ||||||
| rs1045642 | ABCB1 | c.3435C > T |
NS CBZ/CBZE ratio in subjects on concomitant PHT/PB CBZ/CBZE ratio in subjects on concomitant PHT/PB NS |
|||
| rs2032582 | c.2667G > T | |||||
| rs10234411 | 2,481 + 882A > T | |||||
| rs1128503 | ||||||
| c.1236 T > C | ||||||
| Caruso et al. 2014 26 | Italian | 50 | rs1051740 | EPHX1 | c.337 T > C |
NS NS |
| rs2234922 | c.416A > G | |||||
| rs35599367 | CYP3A4 | *22 | NS | |||
| Zhu et al. 2014 27 | Chinese | 210 | rs35599367 | CYP3A4 | *22 |
NS Lower adjusted levels of CBZ and CBZE |
| rs2242480 | *1G | |||||
| rs776746 | CYP3A5 | *3 | Higher dose adjusted levels of CBZ | |||
| rs1057868 | POR | *28 | NS | |||
| rs2234922 | EPHX1 | c.416A > G |
Lower dose adjusted levels of DiOH‐CBZ and DiOH‐CBZ:CBZE ratio Higher DiOH‐CBZ:CBZE ratio NS |
|||
| rs3738046 | c.128G > C | |||||
| rs1051740 | c.337 T > C | |||||
| Panomvana et al. 2013 28 | Thai | 70 | rs776746 | CYP3A5 | *3 | Trend towards reduced clearance (not significant) |
| Puranik et al. 2013 29 |
African‐American Caucasian |
88 | rs2740574 | CYP3A4 | *1B | Reduced clearance |
| rs776746 | CYP3A5 | *3 | Longer half‐life for CBZ (African Americans) | |||
| rs1051740 | EPHX1 | c.337 T > C |
Lower DiOH‐CBZ:CBZE ratio (African‐Americans) NS |
|||
| rs2234922 | c.416A > G | |||||
| rs7439366 | UGT2B7 | c.802 T > C |
NS NS NS Increased clearance (African‐American) NS |
|||
| rs11302069 | c.1090 + 155delA | |||||
| c.735A > G | ||||||
| rs28365062 | ||||||
| c.372A > G | ||||||
| c.1059C > G | ||||||
| rs28365063 | ||||||
| rs4292394 | ||||||
| rs1045642 | ABCB1 | c.3435C > T |
NS Higher clearance (African‐Americans) NS NS Higher DiOH‐CBZ:CBZE ratio (African‐American) Higher DiOH‐CBZ:CBZE ratio (African‐American) |
|||
| rs1128503 | c.1236 T > C | |||||
| rs2032582 | c.2677G > T | |||||
| rs4148734 | c.702 + 1789C > T | |||||
| rs4148739 | c.2482‐236A > G | |||||
| rs4148740 | ||||||
| c.2686‐1911 T > C | ||||||
| rs2273697 | ABCC2 | c.1249G > A |
Higher clearance (Caucasians) Higher CBZE:CBZ ratio (Caucasian male) Reduced clearance and reduced CBZE:CBZ ratio (African‐American) NS |
|||
| rs3740066 | c.3972C > A | |||||
| rs4148386 | 208‐3523G > A | |||||
| rs8187710 | c.4544G > A | |||||
| rs1523127 | NR1I2 | c.‐131C > A |
NS NS Increased CBZE:CBZ ratio and reduced clearance (African‐American) Reduced clearance Increased clearance (African‐American) Increased CBZE:CBZ ratio |
|||
| rs1523130 | c.‐1,663 T > C | |||||
| rs2461817 | c.‐22‐1425A > C | |||||
| rs3814055 | c.‐1135C > T | |||||
| rs4688040 | c.‐22‐1985G > T | |||||
| rs7643645 | c.‐22‐579A > G | |||||
| Yun et al. 2013 30 | Chinese | 83 | rs1051740 | EPHX1 | c.337 T > C |
NS Higher adjusted plasma CBZ levels |
| c.416A > G | ||||||
| rs2234922 | ||||||
| rs2242480 | CYP3A4 | *1G | NS | |||
| Hung et al. 2012 31 | Taiwanese | 234 | rs1051740 | EPHX1 | c.337 T > C |
Higher maintenance dosage NS |
| rs2234922 | c.416A > G | |||||
| rs7668258 | UGT2B7 | c.‐161 T > C |
NS NS NS NS |
|||
| rs7438135 | c.‐900G > A | |||||
| rs28365062 | c.735A > G | |||||
| rs7439366 | c.802 T > C | |||||
| rs1128503 | ABCB1 | c.1236 T > C |
NS NS NS |
|||
| rs2032582 | c.2677G > T | |||||
| rs1045642 | c.3435C > T | |||||
| rs717620 | ABCC2 | c.‐24C > T |
NS NS |
|||
| c.3972C > T | ||||||
| rs2273697 | ||||||
| Sterjev et al. 2012 32 | North Macedonian | 162 | rs1045642 | ABCB1 | c.3435C > T | Higher CBZ plasma levels |
| Meng et al. 2011 33 | Chinese | 84 | rs1045642 | ABCB1 | c.3435C > T |
Lower plasma CBZ levels NS NS |
| rs1128503 | c.1236 T > C | |||||
| rs2032582 | c.2677G > T | |||||
| Park et al. 2009 34 | Korean | 35 | rs776746 | CYP3A5 | *3 | Reduced clearance |
CBZ: carbamazepine, CBZE: carbamazepine 10,11‐epoxide, DiOH‐CBZ: 10,11‐dihydro‐10,11‐trans‐dihydroxy‐carbamazepine, NS: not significant, PB: phenobarbital, PHT: phenytoin