Association between four microRNA binding site-related polymorphisms and the risk of warfarin-induced bleeding complications.

• DOI: 10.17179/excli2019-1352
• Publication Date: 2019-01-01
• Authors: Maryam Hosseindokht; Mohammadali Borou...; Rasoul Salehi; Ali Mandegary; Hajhosseini Talas...; Leyla Pourgholi; Hamed Zare; Shayan Ziaee; Mohammadreza Sharifi
• Keywords: VKORC1; SNP

Bleeding is the most serious complication of warfarin anticoagulation therapy and known to occur even at patients with therapeutic international normalized ratio (INR) range. Recently, it has been shown that microRNAs play a significant role in pharmacogenetics by regulating genes are critical for drug function. Interaction between these target could be affected single-nucleotide polymorphisms (SNPs) located microRNA-binding sites. This study focused on 3'-untranslated region (3'-UTR) SNPs involved action occurrence bleeding complications an Iranian population receiving warfarin. A total 526 under responding dose maintenance INR range 2.0-3.5 three consecutive blood tests were included study. Four selected 3'-UTR (rs12458, rs7294, rs1868774 rs34669593 GATA4, VKORC1, CALU GGCX genes, respectively) potential disrupt/eliminate or enhance/create site genotyped using simple PCR-based restriction fragment length polymorphism (PCR-RFLP) method. Patients rs12458 AT TT genotypes GATA4 gene had lower risk compared AA genotype (adjusted OR: 0.478, 95% CI: 0.285-0.802, P= 0.005, 0.416, 0.192-0.902, 0.026, respectively). other not significantly associated complications. In conclusion, SNP rs12458A>T 3'UTR incidence warfarin-related INR, likely altering microRNA binding metabolism. Further genetics association studies needed validate findings before they can implemented clinical settings.