Table 4.
Most common functional polymorphisms in human ABCB1, ABCC1/2, and ABCG2: allele frequency and functional effects
| Allele variants | Polymorphism/substitution |
Allele frequency (%)a
|
Functional effects | ||
|---|---|---|---|---|---|
| Caucasian | Asian | African | |||
| ABCB1 | |||||
| 1236C>T | Silent | 34–42 | 60–72 | 15–21 | Affects co-translational folding in nearby amino acids that are essential for ATP-binding and ATP hydrolysis141 |
| 2677G>T/A | A893S/T | 38–47/1–10 | 32–62/3–22 | 15/ND | Affects ABCB1 expression or function, but data are inconsistent27 |
| 3435C>T | Silent | 48–59 | 37–66 | 10–27 | Affects co-translational folding in nearby amino acids, thereby altering substrate specificity24 |
| ABCB1*13 | 1236C>T/2677G>T/3435C>T haplotype | 23–42 | 28–56 | 4.5–8.7 | Affects the inhibition of ABCB1 by a small subset of modulators24 |
| ABCC1 | |||||
| 128G>C | C43S | 1 | Reduced plasma membrane localization, ↓vincristine resistance in transfected cells142 | ||
| 1299G>T | R433S | 1.4 | Changes in transport and resistance143 | ||
| 2012G>T | G671V | 2.8 | Associated with anthracycline-induced cardiotoxicity32 | ||
| ABCC2 | |||||
| 1271A>G | R412G | DJS; ↓ in methotrexate elimination144 | |||
| 1249G>A | V417I | 22–26 | 13–19 | 14 | Changes in ABCC2 expression and localization33,36,43 |
| 3563T>A | V1188E | 4–7 | 1 | Associated with anthracycline-induced cardiotoxicity32 | |
| 4544G>A | C1515Y | 4–9 | Associated with anthracycline-induced cardiotoxicity32 | ||
| ABCG2 | |||||
| 34G>A | V12M | 2–10 | 15–18 | 4–6 | Changes in transport and resistance145,146 |
| 376C>T | Q126stop | 0 | 0.9–1.7 | 0 | Loss of transport activity147 |
| 421C>A | Q141K | 9–14 | 27–35 | 1–5 | Affects the ATP-binding domain, thereby leading to reduced transport activity145,146 |