Table 1. Well-studied genes and variants involved in methotrexate pharmacogenomics.
| Gene | Variant (rs#) | Phenotype (population) (PMID) | No association (population) (PMID) |
|---|---|---|---|
| MTHFR | 677C > T (rs1801133) |
C toxicity/adverse events (pediatric ALL, CML) (16870553 [7]) (16920564 [8]) T toxicity/adverse events (pediatric ALL; NHL; CML; RA, Black; PsA; RA, White; RA, Asian; JIA, White; pediatric ALL, Asian) (12453860 [9], 17488658 [10], 11418485 [11], 18381794 [12], 20472929 [13], 17512587 [14], 16501586 [15], 15051775 [16], 11710708 [17], 20863444 [18], 20595278 [19], 18458567 [20]) C efficacy (pediatric ALL; NHL; CML) (14647408 [21]; 15781665 [22], 17488658 [10], 17512587 [14], 15385937 [23]) |
Toxicity (pediatric ALL; pediatric ALL, Asian; RA, Black, White; RA, Hispanic; Psoriasis; NHL) (12915598 [24], 16439441 [25], 19016697 [26], 20514079 [27], 18368069 [28], 15713801 [29], 16462575 [30], 15781665 [22], 16463153 [31]) Efficacy (psoriasis; NHL; pediatric ALL) (19016697 [26], 16463153 [31], 19827168 [32], 16019535 [33]) |
| MTHFR | 1298A>C (rs1801131) |
A toxicity (RA, White; pediatric ALL)(16439441 [25], 18368069 [28], 17323057 [34]) C toxicity/adverse events (NHL; CML; RA; RA Hispanic; CML) (17488658 [10], 16501586 [15], 16572443 [35], 20514079 [27], 16920564 [8]) A efficacy (RA, White; CML, White) (16572443 [35], 15569990 [36]) C efficacy (RA, Asian; pediatric ALL; CML) (20863444 [18], 14647408 [21], 15385937 [23]) |
Toxicity (RA, Black; RA, White, Black; Psoriasis, PsA, pediatric ALL) (16439441 [25], 18381794 [12], 19016697 [26], 20472929 [13], 16870553 [7], 15713801 [29], 15781665 [22], 17512587 [14]) Efficacy (Psoriasis; pediatric ALL) (19016697 [26], 15781665 [22], 17512587 [14], 16019535 [33]) |
| SLC19A1 | 80G>A (rs1051266) |
A toxicity/adverse events (pediatric ALL; ALL; pediatric ALL, Asian) (12411325 [37], (17264302 [38], 17180579 [39], 20335220 [40]) G toxicity (pediatric ALL, Asian) (16462575 [30]) A efficacy (RA; RA, Asian; ALL) (17325736 [41], 18322994 [42], 20335220 [40], 19827168 [32]) G efficacy (pediatric ALL) (12411325 [37]) |
Toxicity (pediatric ALL, PsA) (12915598 [24], 20472929 [13], 18368069 [28], 16870553 [7], 15713801 [29]) |
| TYMS | 28 bp repeat (rs34743033) |
3R/2R toxicity (CML) (16920564 [8]) 3R/3R reduced efficiacy (pediatric ALL) (11937185 [43], 12972956 [44], 15713801 [29], 14647408 [21], 18096764 [45]) |
Efficacy (RA, White) (20386493 [46], 12651279 [47]) Toxicity (pediatric ALL, CML) (16870553 [7], 16501586 [15]) |
ALL, acute lymphoblastic leukemia; CML, chronic myelogenous leukemia; NHL, non-Hodgkin’s lymphoma; PMID, PubMed identifier; PsA psoriatic arthritis; RA, rheumatoid arthritis.