Association Between Nad(P)H Quinone Oxidoreductase 1 (Nqo1) Gene Methylation/Expression and Bleeding Incidence Among an Iranian Population Undergoing Warfarin Therapy Publisher



Hosseini MS¹ ; Pourgholi L¹ ; Ziaee S¹ ; Pourgholi M² ; Mandegary A³ ; Boroumand M⁵ Show Affiliations
Source: Indian Journal of Hematology and Blood Transfusion Published:2024

Abstract

Increased bleeding tendency is a common and challenging complication of warfarin therapy which results in extensive pharmacogenomic studies in order to develop a personalized dosing approach and minimize the risk of related side effects. Here we aimed to explore the potential role of NQO1 gene expression in warfarin response in a group of Iranian patients. We also evaluated the NQO1 promoter methylation and its association with mRNA expression. A total of 87 patients on warfarin therapy including 34 cases with drug-induced bleeding events and 53 matched controls without bleedings were included in the study. The expression of NQO1 was examined by real-time q-PCR and the methylation status of its promoter region was analyzed using methyQESD technique. There was a significant association between the reduced NQO1 gene expression and susceptibility to bleeding before (OR = 1.92, 95% CI = 1.23–3.00, p = 0.004) and following adjustment for hypertriglyceridemia (OR = 2.22, 95% CI = 1.33–3.69, p = 0.002). Furthermore, a medium negative correlation was observed between NQO1 expression and its promoter methylation (r = − 0.382, p = 0.001). The lower expression of NQO1 which partly arises from increased methylation of promoter region, may predispose warfarin treated patients to bleeding events. © The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2024.