Relationship between ITPA polymorphisms and hemolytic anemia in HCV-infected patients after ribavirin-based therapy: a meta-analysis.

Abstract

BACKGROUND:

There is growing evidence that variations in the gene encoding inosine triphosphate pyrophosphohydrolase (ITPase), known as inosine triphosphatase (ITPA), are related to hemolytic anemia, which is frequently observed among hepatitis C virus (HCV)-infected patients receiving ribavirin (RBV)-based therapy. We performed a meta-analysis of all eligible studies assessing ITPA gene polymorphisms related to RBV-induced hemolytic anemia in HCV-infected patients published in PubMed, Embase and the Cochrane library prior to the end of 2014.

METHODS:

Three outcomes were evaluated: (1) hemoglobin decline, (2) severe anemia, and (3) RBV dose reduction or treatment discontinuation. Pooled odds ratio (OR) and 95 % confidence interval (95 % CI) were estimated by either fixed or random effects models.

RESULTS:

Twenty-nine studies were selected from the literature search: 20 references involving 6533 individuals for hemoglobin decline, 13 references on 3764 patients for severe anemia, and 16 references on 3918 patients for RBV dose reduction or discontinuation. Significant associations with hemoglobin decline were found for rs1127354 CC [OR = 12.84 (95 % CI 7.44; 22.17)], rs7270101 AA [OR = 3.41 (95 % CI 2.08; 5.59)] and rs6051702 AA [OR = 4.43 (95 % CI 2.80; 7.00)] genotypes. Moreover, significant associations with hemoglobin decline were also found for absent [OR = 6.01 (95 % CI 4.84; 7.46)] and mild [OR = 4.68 (95 % CI 2.83; 7.74)] ITPase deficiency haplotypes. The ITPA rs1127354 CC genotype and absent ITPase deficiency haplotype were also associated with severe anemia {[OR = 7.77 (95 % CI 5.03; 12.00)] and [OR = 4.79 (95 % CI 1.69; 13.56)], respectively}. Additionally, the rs1127354 CC genotype showed significant association with RBV dose reduction or stopping treatment (OR = 2.24; 95 % CI 1.79; 2.81).

CONCLUSIONS:

ITPA polymorphisms increase the likelihood of developing hemolytic anemia for HCV-infected patients on RBV-based therapy, particularly rs1127354 CC and rs7270101 AA genotypes, suggesting the utility of screening for ITPA polymorphisms to avoid hematological toxicity and increase adherence to RBV-based therapy.

• Authors: Daniel Pineda-Tenor, Mónica García-Álvarez, María A Jiménez-Sousa, Sonia Vázquez-Morón, Salvador Resino
• Journal: Journal of translational medicine (J Transl Med) Vol. 13 Pg. 320 (Oct 06 2015) ISSN: 1479-5876 [Electronic] England
• PMID: 26438033 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Hemoglobins
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• Pyrophosphatases
• ITPA protein, human
• peginterferon alfa-2b
• peginterferon alfa-2a

Topics

• Aged
• Anemia, Hemolytic (chemically induced, genetics)
• Antiviral Agents (adverse effects)
• Female
• Genetic Variation
• Genotype
• Haplotypes
• Hemoglobins (analysis)
• Hepacivirus
• Hepatitis C
• Hepatitis C, Chronic (genetics)
• Humans
• Interferon alpha-2
• Interferon-alpha (adverse effects)
• Male
• Metabolism, Inborn Errors (genetics)
• Middle Aged
• Odds Ratio
• Polyethylene Glycols (adverse effects)
• Polymorphism, Single Nucleotide
• Pyrophosphatases (deficiency, genetics)
• Recombinant Proteins (adverse effects)
• Regression Analysis
• Ribavirin (adverse effects)
• Treatment Outcome