Details

Autor(en) / Beteiligte

• Lin, Jennifer J.
• Loucks, Catrina M.
• Trueman, Jessica N.
• Drögemöller, Britt I.
• Wright, Galen E.B.
• Yoshida, Eric M.
• Ford, Jo-Ann
• Lee, Samuel S.
• Kim, Richard B.
• Al-Judaibi, Bandar
• Schwarz, Ute I.
• Ramji, Alnoor
• Tam, Edward
• Ross, Colin J.
• Carleton, Bruce C.

Titel

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

Ist Teil von

• Biomedicine & pharmacotherapy, 2021-11, Vol.143, p.112195-112195, Article 112195

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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). 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.