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From SNPedia

Geno Mag Summary
(A;A) 3.2 Causative for ITPase deficiency; also, reduces risk of anemia due to ribivarin anti-hepatitis C virus therapy
(A;C) 2 lower ITPA production; be aware if treated with mercaptopurine
(C;C) 0 common in clinvar
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (old)rs1127354
1000 genomesrs1127354
23andMe allrs1127354
SNP Nexus

GWAS Ctlgrs1127354
Max Magnitude3.2
rs1127354 (Pro32Thr/P32T, 94C>A) is a SNP within the ITPA (Inosine triphosphate pyrophosphatase) gene.

[PMID 18685564OA-icon.png] (note: rs1127354 supersedes rs41320251) abolishes ITPA activity in homozygous individuals and reduces the activity to 25% in heterozygous subjects, mercaptopurine metabolism (sig. higher methyl mercaptopurine nucleotides levels + higher probability of severe febrile neutropenia in A carriers treated with mercaptopurine)

[PMID 20021291] Genetic polymorphism of inosine-triphosphate-pyrophosphatase influences mercaptopurine metabolism and toxicity during treatment of acute lymphoblastic leukemia individualized for thiopurine-S-methyl-transferase status

[PMID 20637204] ITPA Polymorphism Affects Ribavirin-induced Anemia and Outcome of Therapy - a Genome-wide Study of Japanese HCV Patients

[PMID 21246582] Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir

[PMID 21274861OA-icon.png] Inosine triphosphatase genetic variants are protective against anemia during antiviral therapy for HCV2/3 but do not decrease dose reductions of RBV or increase SVR

[PMID 21628662OA-icon.png] IL28B But Not ITPA Polymorphism Is Predictive of Response to Pegylated Interferon, Ribavirin, and Telaprevir Triple Therapy in Patients With Genotype 1 Hepatitis C

[PMID 21659334] Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C

? (A;A) (A;C) (C;C)
[PMID 22052220] Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin-induced anemia in chronic hepatitis C patients

[PMID 22118055] Single and combined IL28B, ITPA and SLC28A3 host genetic markers modulating response to anti-hepatitis C therapy

[PMID 22460221] Anemia and thrombocytosis induced by ribavirin monotherapy in patients with chronic hepatitis C

[PMID 22571903] Gene expression profiles associated with anaemia and ITPA genotypes in patients with chronic hepatitis C (CH-C)

[PMID 21703177OA-icon.png] Genome-wide association study of interferon-related cytopenia in chronic hepatitis C patients

Risk Rs1127354(A;A) rs1127354(G;G)
Alt Rs1127354(A;A) rs1127354(G;G)
Reference Rs1127354(C;C)
Significance Other
Disease Inosine triphosphatase deficiency peginterferon alfa-2b and ribavirin response - Toxicity/ADR interferon alfa-2b
Variation info
CLNDBN Inosine triphosphatase deficiency peginterferon alfa-2b and ribavirin response - Toxicity/ADR interferon alfa-2b, recombinant and ribavirin response - Dosage, Toxicity/ADR
Reversed 0
HGVS NC_000020.10:g.3193842C>A
CLNSRC OMIM Allelic Variant PharmGKB Clinical Annotation UniProtKB (protein)
CLNACC RCV000015867.28, RCV000211370.1, RCV000223768.1,

[PMID 17186469OA-icon.png] Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia.

[PMID 18662289OA-icon.png] Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.

[PMID 19193698OA-icon.png] Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate.

[PMID 20547162OA-icon.png] Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia and decrease the need for ribavirin dose reduction.

[PMID 20977565] ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C.

[PMID 21503919] Common genetic polymorphism of ITPA gene affects ribavirin-induced anemia and effect of peg-interferon plus ribavirin therapy.

[PMID 22028438] Impact of inosine triphosphatase gene variants on the risk of anemia in HIV/hepatitis C virus-coinfected patients treated for chronic hepatitis C.

[PMID 22158703OA-icon.png] Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia in HIV/HCV-coinfected patients with all HCV genotypes.

[PMID 22181672] Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype.

[PMID 22406654] Inosine triphosphatase polymorphisms and ribavirin pharmacokinetics as determinants of ribavirin-associate anemia in patients receiving standard anti-HCV treatment.

[PMID 22430973OA-icon.png] Association of ITPA gene polymorphisms and the risk of ribavirin-induced anemia in HIV/hepatitis C virus (HCV)-coinfected patients receiving HCV combination therapy.

[PMID 22613675] Comparison of three different methods for the evaluation of IL28 and ITPA polymorphisms in patients infected with HCV.

GET Evidence
aa_change Pro32Thr
aa_change_short P32T
impact pharmacogenetic
qualified_impact Low clinical importance, pharmacogenetic
overall_frequency 0.0609779
summary This variant is associated with inosine triphosphate pyrophosphohydrolase deficiency and may be associated with an adverse reaction to thiopurine drugs (which are used as immunosuppressants). Homozygotes have no detectable ITPase activity, individuals compound heterozygous with another less severe mutation also have severely reduced enzyme activity.

[PMID 23139603OA-icon.png] Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C

Hepatitis C Treatment Side Effects

[PMID 23195617] Impact of genetic SLC28 transporter and ITPA variants on ribavirin serum level, hemoglobin drop and therapeutic response in patients with HCV infection

[PMID 23538996OA-icon.png] Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients

GWAS snp
PMID [PMID 20173735]
Trait Chronic Hepatitis C infection
Title ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C.
Risk Allele A
P-val 2E-58
Odds Ratio NR NR

[PMID 23933495] Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients

[PMID 24621321OA-icon.png] Severe thrombocytopenia in a patient with inosine triphosphatase (ITPA)-CC genotype caused by pegylated interferon (IFN)-alpha-2a with ribavirin therapy: a case report

[PMID 22584257] Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort.

[PMID 22585729OA-icon.png] ITPA gene polymorphisms significantly affect hemoglobin decline and treatment outcomes in patients coinfected with HIV and HCV.

[PMID 23133602OA-icon.png] Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

[PMID 23201294] Allelic inhibition of displacement activity: a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms.

[PMID 23297176] Model incorporating the ITPA genotype identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C.

[PMID 23490380] An automated rapid detection system using the quenching probe method for detecting interleukin 28B and inosine triphosphatase single nucleotide polymorphisms in chronic hepatitis C.

[PMID 23730840] Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection.

[PMID 24750345] ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type

[PMID 23707372] Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy

[PMID 24304455] Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy

[PMID 23980585] Relationship between inosine triphosphate genotype and outcome of extended therapy in hepatitis C virus patients with a late viral response to pegylated-interferon and ribavirin

[PMID 25834588OA-icon.png] An Index to Predict Ribavirin-Induced Anemia in Asian Patients With Chronic Genotype 1 Hepatitis C

[PMID 26071337] Role of ITPA and SLC28A2 genes in the prediction of anaemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment

[PMID 24841973] Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population