Gene-drug interactions (data source: DGIdb)
Gene Name Entrez ID Drug Name Chembl ID Interaction Types Sources publications
ITPA 3704 INTERFERON ALFA-2B CHEMBL1201558 PharmGKB
ITPA 3704 CITRIC ACID CHEMBL1261 DrugBank 10592235
ITPA 3704 FOLIC ACID CHEMBL1622 PharmGKB
ITPA 3704 MERCAPTOPURINE CHEMBL1425 PharmGKB

Variant-drug associations (data source: PharmGKB)
Gene Name Variant Alleles Chemical Phenotype Category Significance Notes Sentence Publications Annotation ID
ITPA rs1127354 CC mercaptopurine dosage no No significant difference in median cumulative dose was seen between the genotypes at 2 months (p=0.55), 4 months (p=0.81) or 6 months (p=0.78) of the mercaptopurine maintenance phase. Genotype CC is not associated with dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AA + AC. 26405151 1447682410
ITPA rs1127354 CC mercaptopurine dosage no Genotype CC is not associated with dose of mercaptopurine or methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype AC. 29683944 1449311101
ITPA rs7270101 AA mercaptopurine dosage no Genotype AA is not associated with dose of mercaptopurine or methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AC + CC. 29683944 1449311109
ITPA rs1127354 A mercaptopurine "dosage","toxicity" no as measured by 6-MP dose intensity, which is a measure dose adjustment due to toxicity calculated by the ratio of the prescribed 6-MP dose over the protocol dose of 50 mg/m2/d. Allele A is not associated with decreased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C. 29720126 1449750257
ITPA rs1127354 A methotrexate efficacy no Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C. 29743634 1449557945
ITPA rs1127354 CC folic acid efficacy yes Genotype CC is associated with increased response to folic acid and methotrexate in people with Arthritis, Rheumatoid as compared to genotypes AA + AC. 16947783 769173660
ITPA rs1127354 A methotrexate efficacy no Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C. 19193698 769173671
ITPA rs1127354 A mercaptopurine metabolism/PK yes The A allele was associated with increased methylmercaptopurine nucleotide metabolite concentration in bone marrow leukemia cells. Concentrations were also found to be significantly higher in erythrocytes of patients with an A allele during continuation therapy with mercaptopurine. Allele A is associated with metabolism of mercaptopurine in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C. 18685564 1448106601
ITPA rs1127354 A methotrexate efficacy no Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C. 22450926 827863280
ITPA rs1127354 AA + AC azathioprine efficacy yes After 1 year of low-dose AZA treatment, a significant reduction in SLEDAI score was observed in patients carrying the CA or AA genotypes. The variant was most highly correlated with the change in SLEDAI score (r = 0.354, P = 0.006) in a multivariant analysis. Genotypes AA + AC is associated with increased response to azathioprine in people with Lupus Erythematosus, Systemic as compared to genotype CC. 19129747 1448107984
ITPA rs1127354 AA + AC azathioprine metabolism/PK yes as measured by decreased 6-TGNs compared to those with no ITPA and ABCC4 variants. High 6-TGNs were correlated to low WBC counts and increased likelihood of leukopenia. ie this variant alone probably had lower likelihood of leukopenia but authors did not test significance of this instead grouped double variant with both ABCC4 rs3765534 T and ITPA A for analysis and rs3765534 T had increased risk of leukopenia thus balancing the risk. Genotypes AA + AC is associated with decreased metabolism of azathioprine or mercaptopurine in people with Inflammatory Bowel Diseases as compared to genotype CC. 20393862 1448267671
ITPA rs1127354 AC azathioprine metabolism/PK yes although this variant is lower activity enzyme it results in higher concentrations of MMPN metabolites. TGN/dose ratio was not different for the different genotypes. Genotype AC is associated with increased metabolism of azathioprine in people with Inflammatory Bowel Diseases as compared to genotype CC. 23787247 1448262619
ITPA rs1127354 CC ribavirin dosage yes The total amount of RBV given to each patient was significantly lower in genotype CC patients (median, 70 400 mg) compared with CA/AA patients (median, 97 200 mg) (P < 0.05). Total doses of simeprevir and PEG-IFNa did not differ between ITPA CC and CA/AA groups. Genotype CC is associated with decreased dose of ribavirin. 26916827 1448602976
ITPA rs1127354 C methotrexate toxicity no Discontinuation due to adverse effects. Allele C is not associated with discontinuation of methotrexate in people with Arthritis, Rheumatoid as compared to allele A. 27217051 1449164992
ITPA rs1127354 AA + AC methotrexate efficacy no No significant difference in frequency of genotypes was seen between non-responders (DAS28>=3.2) and those with low disease activity (LDA; DAS28<3.2) when treated with methotrexate for 6 months. Genotypes AA + AC is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype CC. 29520081 1449752227
ITPA rs1127354 A peginterferon alfa-2b efficacy yes This genotype is associated with sustained virological response (SVR). This association was not statistically significant by multivariate analysis (P=0.1). Allele A is associated with increased response to peginterferon alfa-2b and ribavirin in people with Hepatitis C as compared to allele C. 20637204 1444706755
ITPA rs1127354 CC peginterferon alfa-2b efficacy no This genotype is not associated with sustained virological response (SVR). Genotype CC is not associated with response to peginterferon alfa-2b and ribavirin in people with Hepatitis C as compared to genotype AC. 23730840 1444707059
ITPA rs1127354 CC peginterferon alfa-2a efficacy no The authors actually compared platelet counts between patients with normal or deficient ITPase activity. Patients with the composite genotypes of rs1127354 CC and rs7270101 AA had "normal ITPase activity" and all other genotype combinations were classified as "deficient". Univariable logistic regression normal ITPase activity was not significantly associated with virological relapse. Genotype CC is not associated with response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes AA + AC. 26441325 1446905573
ITPA rs7270101 AA peginterferon alfa-2a efficacy no The authors actually compared platelet counts between patients with normal or deficient ITPase activity. Patients with the composite genotypes of rs1127354 CC and rs7270101 AA had "normal ITPase activity" and all other genotype combinations were classified as "deficient". Univariable logistic regression normal ITPase activity was not significantly associated with virological relapse. Genotype AA is not associated with response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes AC + CC. 26441325 1446905582
ITPA rs7270101 AC + CC azathioprine "toxicity","metabolism/PK" yes as measured by higher concentrations of 6-TGNs in RBCs. Genotypes AC + CC is associated with increased metabolism of azathioprine or mercaptopurine in people with Inflammatory Bowel Diseases or Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype AA. 18662289 1448268147