Have questions? Visit https://www.reddit.com/r/SNPedia


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 (classic)rs1127354
1000 genomesrs1127354
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.

[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