Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment.

Abstract

BACKGROUND:

The current use of ribavirin in difficult-to-cure chronic hepatitis C patients (HCV) and patients with severe respiratory infections is constrained by the issue of ribavirin-induced hemolytic anemia that affects 30% of treated patients, requiring dosage modification or discontinuation. Though some genetic variants have been identified predicting this adverse effect, known clinical and genetic factors do not entirely explain the risk of ribavirin-induced anemia.

METHODS:

We assessed the associations of previously identified variants in inosine triphosphatase (ITPA), solute carrier 28A2 (SLC28A2) and vitamin D receptor (VDR) genes with ribavirin-induced anemia defined as hemoglobin decline of ≥30 g/L on treatment, followed by a staged discovery (n = 114), replication (n = 74), and combined (n = 188) genome-wide association study to uncover potential new predictive variants.

RESULTS:

We identified a novel association in the gene coding glycophorin C (rs6741425; OR:0.12, 95%CI:0.04-0.34, P = 2.94 × 10-6) that predicts protection against ribavirin-induced anemia. We also replicated the associations of ITPA and VDR genetic variants with the development of ribavirin-induced anemia (rs1127354; OR:0.13, 95%CI:0.04-0.41, P = 8.66 ×10-5; and rs1544410; OR:1.65, 95%CI:1.01-2.70, P = 0.0437).

CONCLUSIONS:

GYPC variation affecting erythrocyte membrane strength is important in predicting risk for developing ribavirin-induced anemia. ITPA and VDR genetic variants are also important predictors of this adverse reaction.

• Authors: Jennifer J Lin, Catrina M Loucks, Jessica N Trueman, Britt I Drögemöller, Galen E B Wright, Eric M Yoshida, Jo-Ann Ford, Samuel S Lee, Richard B Kim, Bandar Al-Judaibi, Ute I Schwarz, Alnoor Ramji, Edward Tam, Colin J Ross, Bruce C Carleton
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 143 Pg. 112195 (Nov 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34562771 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Antiviral Agents
• Glycophorins
• Receptors, Calcitriol
• VDR protein, human
• Ribavirin
• Pyrophosphatases
• ITPA protein, human

Topics

• Aged
• Anemia, Hemolytic (chemically induced, diagnosis, genetics)
• Antiviral Agents (adverse effects)
• Canada
• Case-Control Studies
• Female
• Genome-Wide Association Study
• Glycophorins (genetics)
• Hepatitis C, Chronic (diagnosis, drug therapy)
• Humans
• Male
• Middle Aged
• Pharmacogenetics
• Pharmacogenomic Testing
• Pharmacogenomic Variants
• Prospective Studies
• Pyrophosphatases (genetics)
• Receptors, Calcitriol (genetics)
• Ribavirin (adverse effects)
• Risk Assessment
• Risk Factors