Gene | SNP ID | SNP allele | Effects on gene product/ enzyme | Clinical significance |
---|---|---|---|---|
MTHFR | rs1801131 | 1298 A > C | Decreases MTHFR activity | Associated with MTX efficacy, not associated with MTX toxicity, or associated with MTX toxicity |
TYMS | rs16430 | 3'-UTR - 6/6 | Decreases TYMS mRNA expression | Associated with MTX toxicity |
RFC1 | rs1051266 | 80 G > A | Affects transcriptional activity of RFC1 gene and MTX entry into cells | Increases MTX-PG concentrations and good clinical response to MTX treatment |
rs1131596 | −43 T > C | Decreases the expression of RFC1 protein | Unknown | |
FPGS | rs10106 | 1994 G > A | Associated with FPGS mRNA expression | Not associated with MTX efficacy/toxicity, or poor response to MTX treatment |
GGH | rs11545078 | 452 C > T | Associated with lower GGH activity, greater accumulation of long-chain MTX-PGs | Not associated with MTX efficacy/toxicity |
rs3758149 | −401 C > T | Associated with greater GGH promotor activity, decrease polyglutamation | Affects MTX toxicity | |
ABCB1 | rs1045642 | 3435 C > T | Decreases stability/expression of mRNA, reduces the activity of efflux transporters | Associated with MTX efficacy |
ABCC2 | rs4148396 | IVS23 + 56 T > C | Affects ABCC2 enzyme activity and MTX efflux from cell | Associated with MTX toxicity (adverse GI effects) |
ABCG2 | rs2231142 | 914 C > A | Increases MTX-PG1/MTX-PG2 concentrations | Associated with MTX toxicity |