ArticleJournal of hepatology2012
Genome-wide association study of interferon-related cytopenia in chronic hepatitis C patients.
Article in Journal of hepatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01726400 (Is Hepcidin a Possible Contributor to Impaired Iron Mobilization and Anaemia in Hepatitis C Patients Treated With Pegylated Interferon Alpha and Ribavirin Therapy? A Pilot Study), which is not on this map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Is Hepcidin a Possible Contributor to Impaired Iron Mobilization and Anaemia in Hepatitis C Patients Treated With Pegylated Interferon Alpha and Ribavirin Therapy? A Pilot Study
Who cites it
19 citing papers in PubMed, 50 citations in OpenAlex.
- Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.Journal of hepatology · 2013Trial
- Trial
- The intersection of epigenetics and immune thrombocytopenia: new insights into disease mechanisms and treatments.Molecular biology reports · 2025Review
- Treatment outcome and germline predictive factors of ropeginterferon alpha-2b in myeloproliferative neoplasm patients.Cancer medicine · 2024Article
- Platelets as a Gauge of Liver Disease Kinetics?International journal of molecular sciences · 2022Review
- Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response.World journal of hepatology · 2018Article
- Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2018Review
- Association between genetic polymorphisms of thePeerJ · 2017Article
- IFNL3/4 genotype is associated with altered immune cell populations in peripheral blood in chronic hepatitis C infection.Genes and immunity · 2016Article
- The ITPA and C20orf194 Polymorphisms and Hematological Changes During Treatment With Pegylated-Interferon Plus Ribavirin in Patients With Chronic Hepatitis C.Hepatitis monthly · 2016Article
- Aplastic anemia and severe pancytopenia during treatment with peg-interferon, ribavirin and telaprevir for chronic hepatitis C.World journal of gastroenterology · 2015Article
- Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C.Human genetics · 2015Article
- An index to predict ribavirin-induced anemia in asian patients with chronic genotype 1 hepatitis C.Hepatitis monthly · 2015Article
- Association between IPTA gene polymorphisms and hematological abnormalities in hepatitis C virus-infected patients receiving combination therapy.Gut and liver · 2015Article
- Genome-wide association studies in Africans and African Americans: expanding the framework of the genomics of human traits and disease.Public health genomics · 2015Review
- ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection.PloS one · 2015Article
- Clinical utility of pharmacogenomics in the management of hepatitis C.Pharmacogenomics and personalized medicine · 2014Review
- Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with peginterferon plus ribavirin.Viruses · 2012Article
- Pharmacogenomics of hepatitis C infections: personalizing therapy.Genome medicine · 2012Review
Corrections and comments
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Authors and funding
30 authors at 15 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsInterferon-alfa (IFN)-related cytopenias are common and may be dose-limiting. We performed a genome wide association study on a well-characterized genotype 1 HCV cohort to identify genetic determinants of peginterferon-α (pegIFN)-related thrombocytopenia, neutropenia, and leukopenia.
methods1604/3070 patients in the IDEAL study consented to genetic testing. Trial inclusion criteria included a platelet (Pl) count ≥80×10(9)/L and an absolute neutrophil count (ANC) ≥1500/mm(3). Samples were genotyped using the Illumina Human610-quad BeadChip. The primary analyses focused on the genetic determinants of quantitative change in cell counts (Pl, ANC, lymphocytes, monocytes, eosinophils, and basophils) at week 4 in patients >80% adherent to therapy (n=1294).
results6 SNPs on chromosome 20 were positively associated with Pl reduction (top SNP rs965469, p=10(-10)). These tag SNPs are in high linkage disequilibrium with 2 functional variants in the ITPA gene, rs1127354 and rs7270101, that cause ITPase deficiency and protect against ribavirin (RBV)-induced hemolytic anemia (HA). rs1127354 and rs7270101 showed strong independent associations with Pl reduction (p=10(-12), p=10(-7)) and entirely explained the genome-wide significant associations. We believe this is an example of an indirect genetic association due to a reactive thrombocytosis to RBV-induced anemia: Hb decline was inversely correlated with Pl reduction (r=-0.28, p=10(-17)) and Hb change largely attenuated the association between the ITPA variants and Pl reduction in regression models. No common genetic variants were associated with pegIFN-induced neutropenia or leucopenia.
conclusionsTwo ITPA variants were associated with thrombocytopenia; this was largely explained by a thrombocytotic response to RBV-induced HA attenuating IFN-related thrombocytopenia. No genetic determinants of pegIFN-induced neutropenia were identified.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.