Effects of inflammatory cytokine gene polymorphisms on warfarin maintenance doses in Korean patients with mechanical cardiac valves

Abstract

Cytokines that are involved in inflammation are related to blood coagulation, which could indirectly affect warfarin dose requirements. This study aimed to examine the effects of inflammatory cytokine gene polymorphisms on warfarin dose requirements for Korean patients with mechanical heart valves. In total, 191 patients with mechanical heart valves who were on warfarin anticoagulation therapy and maintained INR levels of 2-3 for three consecutive occasions were retrospectively followed up. In addition to vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 (CYP) 2C9 polymorphisms, the interferon-γ, interleukin-1β (IL1B), interleukin-6, interleukin-10, transforming growth factor-β1 (TGFB1), tumor necrosis factor-α, and C-reactive protein genotypes were determined. The predictive contribution of age, VKORC1, and CYP2C9 to variability was 46.0 %. The addition of IL1B and TGFB1 polymorphisms increased the R (2) to 48.8 % for stable dose requirements, and significantly higher doses were found, especially when the TGFB1 CC genotype was combined with the IL1B TT genotype. Based on the results, it was concluded that inflammatory cytokine genes, such as TGFB1 and IL1B, can be predictive variables for stable warfarin doses in Korean patients.

Warfarin Dose Requirements in Adults Hospitalized With COVID-19 Infection: A Retrospective Case Series

“…It has previously been reported that warfarin dose requirements may be reduced in pro-inflammatory states. 15,21 In patients hospitalized with COVID-19, D-dimer, ferritin, and CRP are predictive of severity of illness and mortality. 22,23 Presence of a pro-inflammatory state represented by these markers may have contributed to the IP warfarin sensitivity and decreased dose requirements reported here.…”

Determination of Pleiotropic Effect of Warfarin in VKORC1 and CYP2C9 Genotypes in Patients With Heart Valve Replacement

“…Warfarin is considered to affect the inflammatory pathway in addition to its anticoagulant action (4,5). The dichotomic effect of warfarin means that at high concentrations, i.e., >200 mM of warfarin, high levels of interleukin-6 (IL-6) were observed in macrophage cells, therefore acting as pro-inflammatory, whereas at low warfarin concentrations, i.e., < 200 mM, there was inhibited tumor necrosis factor-α (TNF-α)-induced IL-6 release.…”