Table 2.
Clinically relevant genetic polymorphisms of Phase I (CYP450), Phase II (conjugation) drug metabolism and drug transporters.
| Protein (Gene) | Allelic Variant | Phenotype Prevalence (%) | Relevant effects | ||
|---|---|---|---|---|---|
| CA | AA | AS | |||
| Phase I Enzymes (CYP450) | |||||
| CYP1A2 | 1A2*1C | 0.08 | 0.40 | 0.24 | Association of increased tardive dyskinesia with antipsychotics |
| CYP2B6 | 2B6*4 2B6*6 |
0.04 0.25 |
0.00 0.3–0.5 |
0.07 0.17 |
|
| CYP2C9 | 2C9*2 2C9*3 |
6–8 6–9 |
ND ND |
0 2–3 |
Reduced substrate specificity |
| CYP2C19 | 2C19*2 2C19*3 |
13 0 |
13 ND |
12–30 6–10 |
Inactive enzymatic activity |
| CYP2D6 | 2D6*2xN 2D6*4 2D6*5 2D6*10 2D6*17 |
2–5 15–20 5–7 2 0 |
2 2 4 6 34 |
2 1 6 50 ND |
Increased 2D6 activity (EMs) Inactive enzyme (PMs) No 2D6 enzyme Enzyme instability Reduced substrate affinity |
| CYP3A4 | 3A4*1B | 4 | 82 | 1–2 | Reduced enzyme expression; increased risk of prostate cancer |
| Phase II Enzymes | |||||
| NAT | NAT2*5B NAT2*6A |
50 | 50 | 15 | Slow acetylation of isoniazid, sulfamethoxazole, caffeine; possible modulation of risk for lung, bladder, breast and colon cancers |
| GST | GSTM1*A | 30–62 | 23–48 | 30–60 | Decreased GST activity; possible increased TD severity in GSTP1 polymorphism |
| UGT1A | UGT1A1*28 | 0.5–10 | ND | 3 | Lamotrigine, irinotecan; decreased clearance of tolbutamide, rifampin, haloperidol Elevations in bilirubin |
| TPMT | TPMT*3 | 3.2–10 | 1–10 | 4 | No TPMT activity; Increased toxicity associated with 6-mercaptopurine |
| Drug Transporters | |||||
| P-glycoprotein, MDR1 (ABCB1) | C3435T G2667T |
22–56 | 20 | 50–60 | |
| OATP1B1 (SLCO1B1) | V174A | 13 | 2 | 12 | Statins (increased risk of myopathy); rifampin (inhibitor) |
CA, Caucasian; AA, African American; AS, Asian
EMs, Extensive metabolizers; PMs, Poor metabolizers