TABLE 1.
Information on genes to be tested.
| Genotype/locus | ADR and drug efficacy correlation | Main drug involved | PharmGKB evidence level |
|---|---|---|---|
| CYP2D6 (rs1065852, rs1135822, rs16947, rs28371725, and rs28371735) | ADR correlation: ultra-fast metabolizers (activity score > 2.25) should not use codeine or tramadol as they are prone to serious toxicity risks (Crews et al., 2021) | Codeine Tramadol |
1A |
| Dose-related: individuals with CYP2D6 metabolic disorders (activity score 0) should avoid using codeine and tramadol; intermediate metabolizers (activity score 0.25–1) should use the recommended dosage in the instruction manual. If ineffective, alternative analgesics should be used; recommended dosage in the user manual for CYP2D6 normal metabolizers (activity score 1.25–2.25) (Crews et al., 2021) | |||
|
CYP3A5*3
(rs776746) |
ADR correlation: compared with patients with CYP3A5 * 1/* 1 and * 1/* 3 genotypes, patients with * 3/* 3 genotypes have an increased risk of adverse events after taking fentanyl (Nakatsu et al., 2024) | Fentanyl Oxycodone |
3 |
| Dose-related: compared with patients with CYP3A5 * 1/* 1 or * 1/* 3 genotypes, patients with * 3/* 3 genotypes require an increased dose of oxycodone (Naito et al., 2013) | |||
| ABCB1 (rs1045642) | ADR correlation: Patients with AA genotypes are more likely to experience respiratory depression when using fentanyl than those with AG or GG genotypes (Zhao et al., 2019) | Fentanyl Oxycodone Morphine |
3 |
| Dose-related: Patients with TT genotypes have stronger analgesic effects and lower demand for oxycodone treatment than those with CT or CC genotypes (Lotsch et al., 2009) Patients with TT genotypes have stronger analgesic effects and reduced demand when treated with morphine than those with CT or CC genotypes, but there are opposite conclusions (Campa et al., 2008) | |||
|
OPRM1
(rs1799971) |
ADR correlation: Patients with AA genotypes are more likely to experience ADRs, including allergic reactions and respiratory depression, when using oxycodone and morphine than those with AG or GG genotypes (Zheng et al., 2021; Olsen et al., 2019) | Oxycodone Morphine Fentanyl Tramadol Codeine |
3 |
| Dose correlation: Patients with AA genotypes have better analgesic effects on oxycodone, morphine, and tramadol than those with AG or GG genotypes; related to the analgesic effect of fentanyl, but with opposite conclusions (Jones et al., 2019; Takemura et al., 2024) |
Note: The sequence changes in the CYP2D6 * 10 allele are mainly due to rs1065852, whose mutation can lead to a decrease in CYP2D6 enzyme activity; however, if activity scoring is performed, five SNP sites in the table need to be tested.