Gene-drug interactions (data source: DGIdb)
Gene Name Entrez ID Drug Name Chembl ID Interaction Types Sources publications
MTHFR 4524 MERCAPTOPURINE CHEMBL1425 NCI 16614955
MTHFR 4524 VINORELBINE TARTRATE CHEMBL3039595 PharmGKB
MTHFR 4524 DACTINOMYCIN CHEMBL1554 PharmGKB
MTHFR 4524 CYCLOPHOSPHAMIDE CHEMBL88 PharmGKB
MTHFR 4524 CARBOQUONE CHEMBL443014 PharmGKB
MTHFR 4524 DOCETAXEL CHEMBL92 PharmGKB
MTHFR 4524 NITROUS OXIDE CHEMBL1234579 PharmGKB
MTHFR 4524 BEVACIZUMAB CHEMBL1201583 PharmGKB
MTHFR 4524 PEMETREXED DISODIUM CHEMBL1200373 PharmGKB
MTHFR 4524 CYANOCOBALAMIN CHEMBL2110563 cofactor PharmGKB, DrugBank 20589617, 11979347
MTHFR 4524 GEMCITABINE CHEMBL888 PharmGKB
MTHFR 4524 VINCRISTINE CHEMBL90555 PharmGKB
MTHFR 4524 TETRAHYDROFOLATE CHEMBL2074655 cofactor DrugBank 10208491, 16950805, 10024094, 10233370, 16929515, 10893069, 10196703, 17636160
MTHFR 4524 IRINOTECAN CHEMBL481 NCI 16456808
MTHFR 4524 PHENYTOIN CHEMBL16 NCI 10563481
MTHFR 4524 ZINC SULFATE CHEMBL1200929 NCI 14607573
MTHFR 4524 CARBOPLATIN CHEMBL1351 PharmGKB
MTHFR 4524 PACLITAXEL CHEMBL428647 PharmGKB
MTHFR 4524 BUSULFAN CHEMBL820 PharmGKB
MTHFR 4524 ALBUMIN HUMAN CHEMBL1201451 NCI 11531629
MTHFR 4524 ALCOHOL CHEMBL545 NCI 15894672
MTHFR 4524 OXALIPLATIN CHEMBL414804 NCI 16187112
MTHFR 4524 WARFARIN CHEMBL1464 NCI 14723717
MTHFR 4524 FLUOROURACIL CHEMBL185 CIViC 18704422, 26693073

Variant-drug associations (data source: PharmGKB)
Gene Name Variant Alleles Chemical Phenotype Category Significance Notes Sentence Publications Annotation ID
MTHFR rs1801133 AG + GG methotrexate efficacy yes "MTHFR 677TT ... associated with over 4-fold increased risk for nonresponse. " Alleles complemented to plus chromosomal strand. Genotypes AG + GG is associated with increased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype AA. 24967362 1451258160
MTHFR rs1801133 AG methotrexate efficacy no Please note: alleles have been complemented to the plus chromosomal strand. Genotype AG is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype GG. 24624914 1184467438
MTHFR rs1801133 AA methotrexate efficacy no Please note: alleles have been complemented to the plus chromosomal strand. Genotype AA is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype GG. 24624914 1184467478
MTHFR rs1801133 AA + AG methotrexate "toxicity","metabolism/PK" yes Half life and AUC was significantly increased and elimination rate, volume of distribution and total body clearance was significantly decreased. Genotypes AA + AG is associated with increased exposure to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG. 21644011 1446898629
MTHFR rs1801133 AA methotrexate efficacy yes Authors say this variant is associated with non-response in recessive model (minor allele/minor allele vs minor/major + major major and describe variant as C677T). Alleles complemented to plus chromosomal strand. Genotype AA is associated with decreased response to methotrexate in children with Arthritis, Juvenile Rheumatoid as compared to genotypes AG + GG. 29589488 1449270224
MTHFR rs1801133 GG mercaptopurine dosage no Genotype GG is not associated with dose of mercaptopurine or methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AA + AG. 29683944 1449311087
MTHFR rs1801131 TT mercaptopurine dosage no Genotype TT is not associated with dose of mercaptopurine or methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes GG + GT. 29683944 1449311094
MTHFR rs1801133 A Platinum compounds efficacy no Patients were treated with cisplatin or carboplatin in combination with a third-generation drug (gemcitabine, paclitaxel, pemetrexed or vinorelbine). No significant association with overall response rate (ORR), overall survival (OS) or progression-free survival (PFS) was found for this SNP. Please note that alleles have been complemented to the plus chromosomal strand. Allele A is not associated with response to Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to allele G. 29662106 1449752428
MTHFR rs1801133 AA + AG disulfiram efficacy yes The drop in percentage of cocaine-positive urines for patients with the CT and TT genotypes over the 10 weeks of disulfiram treatment was significantly greater compared to those with the CC genotype. Please note alleles have been complemented to the positive chromosomal strand. Genotypes AA + AG are associated with increased response to disulfiram in people with Cocaine-Related Disorders as compared to genotype GG. 23335901 981502284
MTHFR rs1801133 A methotrexate efficacy no Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G. 21931346 1448108002
MTHFR rs1801131 T methotrexate no Allele T is not associated with response to methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G. 17512587 637879752
MTHFR rs1801131 G fluorouracil efficacy yes Allele G is associated with increased response to fluorouracil, leucovorin and oxaliplatin in people with Colorectal Neoplasms as compared to allele T. 20078613 769166385
MTHFR rs1801133 A fluorouracil efficacy yes Allele A is associated with increased response to fluorouracil, leucovorin and oxaliplatin in people with Colorectal Neoplasms as compared to allele G. 20078613 769166388
MTHFR rs1801133 A methotrexate efficacy no Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G. 19193698 769173669
MTHFR rs1801131 G folic acid efficacy no Allele G is not associated with response to folic acid, hydroxychloroquine, methotrexate and sulfasalazine in people with Arthritis, Rheumatoid. 18322994 769171245
MTHFR rs1801133 A folic acid efficacy no Allele A is not associated with response to folic acid, hydroxychloroquine, methotrexate and sulfasalazine in people with Arthritis, Rheumatoid. 18322994 769171242
MTHFR rs1801131 GT + TT methotrexate efficacy yes Genotypes GT + TT is associated with increased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype GG. 26616421 1447674471
MTHFR rs1801131 GG + GT oxaliplatin efficacy yes Statistics given as trend for increased overall relative response per MTHFR 1298C allele comparing patients receiving 5FU and FOLFOX. Genotypes GG + GT are associated with increased response to oxaliplatin in people with Colorectal Neoplasms as compared to genotype TT. 20385995 769261454
MTHFR rs1801131 TT methotrexate efficacy no In this study those with a "favourable" MTHFR genotype (ie. 677CC/ rs1801133 or 1298AA/rs1801131) were treated with a higher dose. Genotype TT is associated with increased dose of methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes GG + GT. 21747412 827698232
MTHFR rs1801133 GG methotrexate efficacy no In this study those with a "favourable" MTHFR genotype (ie. 677CC/ rs1801133 or 1298AA/rs1801131) were treated with a higher dose. Genotype GG is associated with increased dose of methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AA + AG. 21747412 827698212
MTHFR rs1801133 GG methotrexate efficacy no Also, with increasing copies of rs1801133 G, there was also an increase in the association between rs1801131 and methotrexate response. Genotype GG is associated with increased response to methotrexate in people with Arthritis, Rheumatoid. 16572443 981477479
MTHFR rs1801133 AA benazepril efficacy no No significant difference in the change of systolic blood pressure between baseline and after 15 days of benazepril treatment was seen between the genotypes. Please note alleles have been complemented to the plus chromosomal strand. Genotype AA is not associated with response to benazepril in people with Hypertension as compared to genotypes AG + GG. 15226090 982034384
MTHFR rs1801133 AA benazepril efficacy yes Patients with the AA genotype had a greater change in diastolic blood pressure between baseline and after 15 days of treatment, compared to those with the AG and GG genotypes. Please note alleles have been complemented to the plus chromosomal strand. Genotype AA is associated with increased response to benazepril in people with Hypertension as compared to genotypes AG + GG. 15226090 982034374
MTHFR rs1801131 GT methotrexate efficacy no Please note: alleles have been complemented to the plus chromosomal strand. Genotype GT is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype GG. 24624914 1184467445
MTHFR rs1801131 GT methotrexate efficacy no Please note: alleles have been complemented to the plus chromosomal strand. Genotype GT is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype TT. 24624914 1184467472
MTHFR rs1801131 TT methotrexate efficacy no Please note: alleles have been complemented to the plus chromosomal strand. Genotype TT is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype GG. 24624914 1184467466
MTHFR rs1476413 CC + CT methotrexate efficacy no Those with the CC and CT genotype were more likely to be a responder to treatment. The association was not significant after multiple comparison correction. Genotypes CC + CT is associated with increased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype TT. 25084201 1184748734
MTHFR rs1801131 GG methotrexate metabolism/PK no GG vs TT and GT vs TT were not statistically significant. Genotype GG is not associated with increased concentrations of methotrexate in people with Burkitt Lymphoma, Lymphoma, T-Cell and Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT. 25303299 1296598918
MTHFR rs1801133 AA capecitabine efficacy yes FOLFOX (54.4%) and CAPOX (45.6%) regimens. Measured as cumulative survival over 100 months since diagnosis. Genotype AA is associated with decreased response to capecitabine, fluorouracil, leucovorin and oxaliplatin in people with Colonic Neoplasms as compared to allele G. 24980946 1447521075
MTHFR rs1801131 G methotrexate efficacy no Allele G is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele T. 21931346 1448107993
MTHFR rs1801133 AG methotrexate efficacy yes Alleles were given as C and T. Response measured as relapse-free survival and overall survival. Genotype AG is not associated with response to methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG. 27409003 1448126187
MTHFR rs1801133 GG capecitabine metabolism/PK yes as measured by increase in elimination half-life of capecitabine. Genotype GG is associated with increased exposure to capecitabine in people with Neoplasms as compared to genotypes AA + AG. 26242222 1447944969
MTHFR rs1801131 GT methotrexate efficacy yes Alleles given as C and A. Efficacy of treatment was measured as change of DAS28 from start of treatment to 6months after initiation of treatment. Effect seen in patients receiving monotherapy for methotrexate. In combination with MTHFR A1298C, patients with 677CC-1298CC or 677TT-1298AA had better response to methotrexate by DAS28 change. (p=0.013). Genotype GT is associated with decreased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype TT. 25618758 1447981047
MTHFR rs1801133 AG methotrexate efficacy yes Alleles given as C and T. Efficacy of treatment was measured as change of DAS28 from start of treatment to 6months after initiation of treatment. Effect seen in patients receiving monotherapy for methotrexate. In combination with MTHFR A1298C, patients with 677CC-1298CC or 677TT-1298AA had better response to methotrexate by DAS28 change. (p=0.013). Genotype AG is associated with decreased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotypes AA + GG. 25618758 1447981032
MTHFR rs1801131 GG methotrexate efficacy yes Genotype GG is associated with decreased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotypes GT + TT. 27992285 1448592688
MTHFR rs1801131 G folic acid metabolism/PK not stated Please note that alleles have been complemented to the positive stand. Case study of a patient with the A allele at rs1801133 and the G allele at rs1801131 who subsequently responded to folate supplementation. Allele G is associated with decreased metabolism of folic acid. 29317847 1449296305
MTHFR rs1801133 A folic acid metabolism/PK not stated Please note that alleles have been complemented to the positive stand. Case study of a patient with the A allele at rs1801133 and the G allele at rs1801131 who subsequently responded to folate supplementation. Allele A is associated with decreased metabolism of folic acid. 29317847 1449296299
MTHFR rs1801133 G methotrexate toxicity no Discontinuation due to adverse effects. Please note that alleles have been complemented to the plus chromosomal strand. Allele G is not associated with discontinuation of methotrexate in people with Arthritis, Rheumatoid as compared to allele A. 27217051 1449164930
MTHFR rs1801131 G methotrexate toxicity no Discontinuation due to adverse effects. Please note that alleles have been complemented to the plus chromosomal strand. Allele G is not associated with discontinuation of methotrexate in people with Arthritis, Rheumatoid as compared to allele T. 27217051 1449164936
MTHFR rs1801133 AG l-methylfolate efficacy not stated Please note that alleles have been complemented to the positive strand. Case study of a patient with the AG genotype whose response to pharmacotherapy was improved by the addition of folate supplementation. Genotype AG is associated with increased response to l-methylfolate in men with Bipolar Disorder, Depression and Obsessive-Compulsive Disorder. 27520898 1450814388
MTHFR rs1801133 G risperidone efficacy no Please note that alleles have been complemented to the positive strand. Allele G is not associated with response to risperidone in people with Schizophrenia as compared to allele A. 28696411 1450928209
MTHFR rs1801131 GT l-methylfolate efficacy not stated Please note that alleles have been complemented to the positive strand. Case series of adolescents with treatment-resistant depression who were heterozygous at rs1801131 and/or rs1801133 and responded to folate supplementation to pharmacotherapy. Genotype GT is associated with increased response to l-methylfolate in children with Depressive Disorder, Major. 31058543 1450814400
MTHFR rs17421511 AG + GG methotrexate efficacy no Those with the GG and AG genotype were more likely to be a responder to treatment compared to patients with the AA genotype. The association was not significant after multiple comparison correction. Genotypes AG + GG is associated with increased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype AA. 25084201 1184748726
MTHFR rs1801131 T methotrexate efficacy no Allele T is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G. 19827168 769170786
MTHFR rs1801133 A methotrexate "toxicity","metabolism/PK" no Allele A is not associated with response to methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G. 16462575 769170744
MTHFR rs1801133 A methotrexate efficacy no Allele A is not associated with response to methotrexate in children with Lymphoma, Non-Hodgkin as compared to allele G. 16463153 769170766
MTHFR rs1801133 A methotrexate efficacy no Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G. 19827168 769170776
MTHFR rs1801131 G methotrexate no Allele G is not associated with response to methotrexate in people with Arthritis, Juvenile Rheumatoid. 20595278 769170664
MTHFR rs1801131 G benazepril efficacy yes When in a haplotype with rs1801133 allele G, and where only one copy of this GG haplotype was present. Patients with this haplotype had a significantly lower diastolic and systolic blood pressure (DBP and SBP) response to benazepril between baseline and 15 days of treatment, as compared to those with any other haplotype. Please note: alleles have been complemented to the plus chromosomal strand. Allele G is associated with decreased response to benazepril in people with Hypertension. 16081343 982043429
MTHFR rs1801131 GG methotrexate toxicity no Meta-analysis with 5 studies. Cohorts of pediatrics (3 studies) and adults (2 studies) were also considered separately. No association with risk for experiencing relapse was found when considering the pediatric, adult or overall cohorts. Please note alleles have been complemented to the plus chromosomal strand. Genotype GG is not associated with response to methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes GT + TT. 24637499 1296599948
MTHFR rs1801131 G Platinum compounds efficacy no Patients were treated with cisplatin or carboplatin in combination with a third-generation drug (gemcitabine, paclitaxel, pemetrexed or vinorelbine). No significant association with overall response rate (ORR), overall survival (OS) or progression-free survival (PFS) was found for this SNP. Please note that alleles have been complemented to the plus chromosomal strand. Allele G is not associated with response to Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to allele T. 29662106 1449752421
MTHFR rs1801131 G Vitamin B-complex, Incl. Combinations efficacy yes Please note that allele has been complemented to the positive strand. Patients who carried either the A allele of rs1801133 or the G allele of rs1801131 were recruited into the study (genotypes are not given) and given a capsule containing reduced B vitamins and macronutrients or a placebo. Patients taking the B vitamin capsule showed a significant decrease in MADRS score over 8 weeks of treatment compared to those taking placebo. Allele G is associated with increased response to Vitamin B-complex, Incl. Combinations in people with Depressive Disorder, Major. 27035272 1450814412
MTHFR rs1801133 G benazepril efficacy yes When in a haplotype with rs1801131 allele G, and where only one copy of this GG haplotype was present. Patients with this haplotype had a significantly lower diastolic and systolic blood pressure (DBP and SBP) response to benazepril between baseline and 15 days of treatment, as compared to those with any other haplotype. Please note alleles have been complemented to the plus chromosomal strand. Allele G is associated with decreased response to benazepril in people with Hypertension. 16081343 982043442
MTHFR rs1801133 AA + AG methotrexate metabolism/PK yes AA vs GG and AG vs GG were statistically significant. Genotypes AA + AG is associated with increased concentrations of methotrexate in people with Burkitt Lymphoma, Lymphoma, T-Cell or Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG. 25303299 1296598845
MTHFR rs1801133 AA methotrexate toxicity yes Meta-analysis with 8 studies. Cohorts of pediatrics (6 studies) and adults (2 studies) were also considered separately. In the pediatric and overall cohort, those with the AA genotype had a greater risk of experiencing relapse as compared to those with the AG or GG genotype; no significant result was seen when considering the adult cohort (the authors note that more studies are needed before reliable conclusions can be drawn regarding the influence of rs1801133 on relapse in adults with ALL). Please note alleles have been complemented to the plus chromosomal strand. Genotype AA is associated with decreased response to methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AG + GG. 24637499 1296599938
MTHFR rs1801133 AA methotrexate efficacy no Genotype AA is associated with increased red blood cell folate when treated with methotrexate as compared to genotype GG but this did not correlate with disease activity or red blood cell methotrexate metabolites. Genotype AA is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype GG. 20386493 1448108623
MTHFR rs1801133 AA methotrexate metabolism/PK yes Genotype AA is associated with increased concentrations of methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AG + GG. 17180579 1448109930
MTHFR rs1801133 AA bevacizumab efficacy yes Patients with the AA genotype had decreased progression-free survival and overall survival in multivariable analysis. However, note that these were only a "nominally" significant associations: formally significant was defined as p<0.0026, and nominally significant as p<0.05. No association with response was found. Please note that alleles have been complemented to the plus chromosomal strand. Genotype AA is associated with decreased response to bevacizumab, capecitabine, cisplatin, docetaxel, epirubicin, oxaliplatin or trastuzumab in people with Stomach Neoplasms as compared to genotypes AG + GG. 27995989 1448568276
MTHFR rs1801133 AA + AG fluorouracil efficacy yes Patients receiving fluorouracil-based chemotherapy. Response included complete response (CR) and partial response (PR). Non-response included progressive disease (PD) and stable disease (SD). Please note that alleles have been complemented to the plus chromosomal strand. Genotypes AA + AG is associated with increased response to fluorouracil in people with Colorectal Neoplasms as compared to genotype GG. 29134491 1449147078
MTHFR rs1801133 A Vitamin B-complex, Incl. Combinations efficacy yes Please note that allele has been complemented to the positive strand. Patients who carried either the A allele of rs1801133 or the G allele of rs1801131 were recruited into the study (genotypes are not given) and given a capsule containing reduced B vitamins and macronutrients or a placebo. Patients taking the B vitamin capsule showed a significant decrease in MADRS score over 8 weeks of treatment compared to those taking placebo. Allele A is associated with increased response to Vitamin B-complex, Incl. Combinations in people with Depressive Disorder, Major. 27035272 1450814406