Cytochrome P450 oxidoreductase genetic polymorphisms A503V and rs2868177 do not significantly affect warfarin stable dosage in Han-Chinese patients with mechanical heart valve replacement

摘要

Purpose: To investigate the influence of cytochrome P450 oxidoreductase (POR) polymorphisms (A503V and rs2868177) on warfarin stable dosage (WSD) in Han-Chinese patients with mechanical heart valve replacement (MHVR). Methods: Three hundred and seventeen Han-Chinese MHVR patients on stable maintenance dose of warfarin were enrolled. Blood samples were collected for genotyping analyses of VKORC1 -1639GA, CYP2C93, CYP4F2 rs2108622 and POR (A503V and rs2868177). Average WSD of carriers with variant POR genotypes or haplotypes were compared. Association analyses were performed by single and multiple linear regression analysis. Results: The variant allele frequencies of POR polymorphisms (A503V and rs2868177) were 38.8 % and 44.8 %, respectively. D' between POR A503V and rs2868177 was 0.855, r2 was 0.375, and the frequencies of the four POR haplotypes were 42.3 % for CG, 36.3 % for TA, 18.9 % for CA, and 2.5 % for TG, respectively. There were no significant differences in average WSD among carriers with three variant POR A503V genotypes or among carriers with three variant POR rs2868177 genotypes (both P 0.05). Similarly, there were no significant differences in average WSD among carriers with variant POR haplotypes (all P 0.05). Neither single nor multiple linear regression analyses showed significant effects of POR A503V or POR rs2868177 polymorphisms on WSD. Conclusion: POR polymorphisms (A503V and rs2868177) do not appear to significantly influence WSD in Han-Chinese patients with MHVR.