TABLE 3.
Effect of gene polymorphism on the pharmacokinetics of IM in the regimen of GISTs or CML.
| Number | Gene polymorphism | Dosage of IM | Sample and numbers | Major results | Country | References |
|---|---|---|---|---|---|---|
| 1 | CYP2C19 rs 28399505 (T>C) | 400 mg/d | GISTs, n = 118 | The patients’ plasma level with heterozygote TC was significantly lower than that with the wildtype TT. | China | Qiu et al. (2017) |
| 2 | CYP3A4 rs 2242480 (G>A) | 400 mg/d | GISTs, n = 68 | Patients with the GG genotype showed a significantly higher plasma level than patients with the GA + AA genotype | China | Liu et al. (2017) |
| 3 | CYP3A4 rs 755828176 (G>A) | 400 mg/d | GISTs, n = 62 | CYP3A4 (rs755828176) was significantly associated with unbound IM and NDI plasma trough levels | China | Qian et al. (2019) |
| 4 | CYP3A5-A6986G rs 776746 | 400 mg daily or twice daily | CML, n = 173 | Patients with the GG genotype for CYP3A5-A6986G (p = 0.016) had significantly higher trough levels of IM. | India | Harivenkatesh et al. (2017) |
| 5 | ABCB1 rs1045642 (T>C) | 400 mg/d | GISTs, n = 68 | Patients with the TT + CT genotype showed significantly higher plasma levels than those with the CC genotype | China | Liu et al. (2017) |
| 6 | ABCB1 (1236T, 3435C>T, 2677G>T/A) | 400 mg/d | CML, n = 90 | Among patients who were homozygous for allele 1236T, 85% achieved a major molecular response vs. 47.7% for the other genotypes (p = 0.003). For the 2677 G>T/A polymorphism, the presence of the G allele was associated with a worse response. Patients with a 1236 TT genotype had higher IM concentrations. No association between C3435T polymorphism and response to ABVD was detected among HL patients (p > 0.05). | France | Mhaidat et al. (2011) |
| 7 | ABC1 3435C>T | 400 mg/d | CML, n = 126 | Patient with the TT and GG minor alleles of the SNPs, ABCB1, C3435T, and CYP3A5*3, showed lower clearance when compared with the CC and AA alleles, whereas the CT and AG had a higher clearance than the clearance of IM. | Nigeria | Adeagbo et al. (2017) |
| 8 | ABCB1 3435C>T | 400 mg/d | CML, n = 73 | Patients with this genotype showed no significant difference in the trough-level concentrations | India | Francis et al. (2015) |
| 9 | ABCB1 2677G>T/A | 400 mg/d | CML, n = 73 | Patients with this genotype showed no significant difference in the trough-level concentrations | India | Francis et al. (2015) |
| 10 | ABCG2 (421C>A) | 400 mg/d | CML, n = 82 | The CC, CA, and AA genotypes in ABCG2 421C>A yielded significantly different frequencies for MMR (p = 0.02); there were no statistically significant differences in the trough concentrations | Korea | Seong et al. (2013) |
| 11 | ABCG2 (421C>A) | 400 mg/d | CML, n = 67 | IM trough concentrations were significantly higher in the 25 patients with ABCG2 421C/A or 421A/A than in the 42 patients with 421C/C (p = 0.015) | Japan | Takahashi et al. (2010) |
| 12 | ABCG2 (421C>A) | 400 mg/d | CML, n = 73 | Patients with this genotype showed no significant difference in trough-level concentrations | India | Francis et al. (2015) |
| 13 | NR1I2 rs 3814055 (C>T) | 400 mg/d | GISTs, n = 68 | Patients with the CC genotype showed significantly higher plasma levels than those with the CT + TT genotype | China | Liu et al. (2017) |
| 14 | NR1I2 rs 3814055 (C>T) | 400 mg/d | GISTs, n = 62 | Patients with the CC genotype had significantly higher unbound IM dose-adjusted plasma trough concentrations (p = 0.040) | China | Qian et al. (2019) |
| 15 | IL13 rs1800925 and CXCL14 rs 7716492 | 400 mg/d | GISTs, n = 129 | Mutations of IL13 rs1800925 and CXCL14 rs7716492 were related to the incidence of leukopenia and rash, separately (p < 0.05) | China | Zhang et al. (2018) |
| 16 | SLCO1A2 (-1105 G>A, -1032 G>A) | 400 mg/d | CML, n = 34 | IM clearance in patients with CML was influenced by the SLCO1A2 −1105g>a/−1032g>a genotype (p = 0.075) and the SLCO1A2 -361gg genotype | Japan | Yamakawa et al. (2011b) |
| 17 | SLCO1B3 (334T>G) | 400 mg/d | CML, n = 34 | Patients with genetic SLCO1B3 334T>G polymorphism had increased clearance rate of IM (p = 0.019) | Japan | Yamakawa et al. (2011a) |
| 18 | SLCO1B3 (334T>G) | 400 mg/d | CML, n = 15 | SLCO1B3 334T>G polymorphism could have had a significant impact on the intracellular concentration of IM in leukocytes, but it had no correlation with plasma concentrations | Japan | Nambu et al. (2011) |
| 19 | SLC22A1 (IVS6-878C>A, 1222A>G, IVS7+850C>T) | 400 mg/d | CML, n = 38 | This type of genotype was significantly associated with IM clearance | Singapore | Singh et al. (2012) |
| 20 | hOCT1 (c.480C4G) | 400 mg/d | CML, n = 60 | The c.480C4G genotype of hOCT1 had a significant effect on the apparent IM clearance | Italy | Di Paolo et al. (2014) |
| 21 | hOCT1 M408V (rs628031) | 400 mg/d | CML, n = 106 | M408V were significantly associated with the CCyR and MMR. | India | Vaidya et al. (2015) |
| 22 | OCT1 1386C>A | 400 mg/d | CML, n = 73 | Patients with this genotype showed no significant difference in the trough-level concentrations | India | Francis et al. (2015) |
| 23 | OCT1 1022C>T | 400 mg/d | CML, n = 73 | Patients with the genotype showed no significant difference in the trough-level concentrations | India | Francis et al. (2015) |
| 24 | OCT11222A>G | 400 mg/d | CML, n = 73 | Patients with this genotype showed no significant difference in the trough-level concentrations | India | Francis et al. (2015) |
OCT, organic cation transporter 1; IM, Imatinib mesylate; CML, chronic myeloid leukemia.