ITPA gene polymorphism (<i>94C&gt;A</i>) effects on ribavirin‐induced anemia during therapy in Egyptian patients with chronic hepatitis C

Raziky, Maissa El; Baki, Amin Abdel; Afify, Shimaa; Shahin, Rasha Mohamad Hosny

doi:10.1002/jmv.24844

Cited by 6 publications

(5 citation statements)

References 40 publications

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“…Studies showed that the proportion of patients who completed the planned ribavirin treatment in non‐CC patients was significantly higher than that of patients with CC 30,33 . This result is consistent with the conclusion that the incidence of haemolytic anaemia in patients with non‐CC type ITPA rs1127354 is relatively low, and the level of haemoglobin is reduced.…”

Section: Discussionsupporting

confidence: 84%

Association between inosine triphosphatase rs1127354 polymorphisms and ribavirin‐induced anaemia and outcome in hepatitis C virus‐infected patients: A meta‐analysis

Sun

et al. 2020

J Clin Pharm Ther

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What is known and objectives The association between inosine triphosphatase (ITPA) rs1127354 polymorphisms in HCV‐infected patients receiving ribavirin (RBV)‐based therapy, and the risk of adverse drug reaction and outcomes is still unclear. A meta‐analysis was conducted to summarize and clarify this association systematically. Methods A comprehensive search was performed in PubMed, Embase and Web of Sciences, and twenty‐two studies were selected from the literature search. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were estimated by either fixed‐ or random‐effects models. Results Four outcomes were evaluated: (a) haemoglobin decline: significant associations with haemoglobin decline were found for rs1127354 CC VS CA + AA (OR = 10.59, 95% CI = 6.39‐17.54); (b) severe anaemia: significant association with severe anaemia was observed for rs1127354 CC VS CA + AA (OR = 16.24, 95% CI = 6.21‐42.43); (c) sustained virological response (SVR): CC genotype carriers had a decrease SVR during treatment (OR = 0.65, 95% CI = 0.52‐0.81); (d) RBV dose reduction or stopping treatment: although statistical evidence of an association was found between the polymorphism and RBV dose reduction during treatment (OR = 1.80, 95% CI = 1.03‐3.13), the sensitivity analysis suggested this result was not robust. What is new and conclusion Patients with ITPA rs1127354 CC polymorphism are more likely to develop haemolytic anaemia, severe anaemia and decreased SVR. Testing for this genetic polymorphism may benefit patients.

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Section: Discussionsupporting

confidence: 84%

Association between inosine triphosphatase rs1127354 polymorphisms and ribavirin‐induced anaemia and outcome in hepatitis C virus‐infected patients: A meta‐analysis

Sun

et al. 2020

J Clin Pharm Ther

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“…Table S1 summarises the collection of exonic variants that are more confidently dominance fine-mapped. The non-additive signal in the ITPA locus associated with red blood cell distribution width was fine-mapped to rs1127354, a non-synonymous single nucleotide variant which is known to predict drug induced anaemia among chronic HCV patients (39)(40)(41)(42)(43). The genome-wide significant non-additive association with hearing difficulty/problems was fine-mapped to rs2877561, a synonymous change in ILDR1 associated with age-related hearing impairment (44) but which did not reach genome-wide significance in that study.…”

Section: Application: Fine-mapping Dominance Locimentioning

confidence: 99%

Analysis of genetic dominance in the UK Biobank

Palmer

Zhou

Abbott

et al. 2021

Preprint

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In classical statistical genetic theory, a dominance effect is defined as the deviation from a purely additive genetic effect for a biallelic variant. Dominance effects are well documented in model organisms. However, evidence in humans is limited to a handful of traits, particularly those with strong single locus effects such as hair color. We carried out the largest systematic evaluation of dominance effects on phenotypic variance in the UK Biobank. We curated and tested over 1,000 phenotypes for dominance effects through GWAS scans, identifying 175 loci at genome-wide significance correcting for multiple testing (P < 4.7 × 10-11). Power to detect non-additive loci is much lower than power to detect additive effects for complex traits: based on the relative effect sizes at genome-wide significant additive loci, we estimate a factor of 20-30 increase in sample size will be necessary to capture clear evidence of dominance similar to those currently observed for additive effects. However, these localised dominance hits do not extend to a significant aggregate contribution to phenotypic variance genome-wide. By deriving a version of LD-score regression to detect dominance effects tagged by common variation genome-wide (minor allele frequency > 0.05), we found no strong evidence of a contribution to phenotypic variance when accounting for multiple testing. Across the 267 continuous and 793 binary traits the median contribution was 5.73 × 10-4, with unbiased point estimates ranging from -0.261 to 0.131. Finally, we introduce dominance fine-mapping to explore whether the more rapid decay of dominance LD can be leveraged to find causal variants. These results provide the most comprehensive assessment of dominance trait variation in humans to date.

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“…Retinal hemorrhage is also a typical finding of anemia or thrombocytopenia in retinopathy. IFN-based therapies and RBV have dose-dependent side effects of anemia and thrombocytopenia [22][23][24][25][26][27][28]. Our study revealed a higher incidence of anemia and thrombocytopenia in the HCV-treated cohort.…”

Section: Discussionmentioning

confidence: 59%

Analysis of Different Types of Interferon-Associated Retinopathy in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Plus Ribavirin

Muo

et al. 2021

Viruses

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This retrospective cohort study aims to investigate interferon (IFN)-associated retinopathy incidence in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon (PegIFN) plus ribavirin (RBV). We selected 1688 patients undergoing PegIFN/RBV therapy for HCV (HCV-treated cohort), 3376 patients not receiving HCV treatment (HCV-untreated cohort) and 16,880 controls without HCV (non-HCV cohort) from the Taiwan Longitudinal Health Insurance Database. The patients were frequency-matched by age, sex, and index date at a 1:2:10 ratio, and followed up until the end of 2013. Cox proportional hazard regression models were used to compare the incidences of any retinal vascular events, including subtypes, among the three cohorts. Compared with the non-HCV cohort, the HCV-treated cohort had a significantly increased risk of retinopathy (hazard ratio (HR) = 4.98, 95% confidence interval (CI): 2.02–12.3). The risk was particularly prominent for retinal hemorrhage (HR = 12.7, 95% CI: 3.78–42.9). When the HCV-untreated cohort was used as the reference, the aforementioned HRs increased to 9.02 (95% CI: 3.04–26.8) and 32.3 (95% CI: 3.94–265), respectively. This study suggested that PegIFN/RBV therapy significantly increased the risk of retinal hemorrhage but not retinal vascular occlusions in the HCV-treated cohort.

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ITPA gene polymorphism (94C>A) effects on ribavirin‐induced anemia during therapy in Egyptian patients with chronic hepatitis C

Cited by 6 publications

References 40 publications

Association between inosine triphosphatase rs1127354 polymorphisms and ribavirin‐induced anaemia and outcome in hepatitis C virus‐infected patients: A meta‐analysis

Association between inosine triphosphatase rs1127354 polymorphisms and ribavirin‐induced anaemia and outcome in hepatitis C virus‐infected patients: A meta‐analysis

Analysis of genetic dominance in the UK Biobank

Analysis of Different Types of Interferon-Associated Retinopathy in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Plus Ribavirin

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