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

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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.

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Authors and Affiliations

  1. Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 120-750, Korea

    In Kyung Yoon, Yun Jung Choi, Kyung Eun Lee, Jeong Yeon Rhie, Byung Koo Lee & Hye Sun Gwak

  2. Department of Thoracic & Cardiovascular Surgery, Yonsei University Health System, Yonseiro 50, Seodaemun-gu, Seoul, 120-752, Korea

    Byung Chul Chang

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  1. In Kyung Yoon
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  4. Kyung Eun Lee
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Correspondence to Hye Sun Gwak.

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In Kyung Yoon and Yun Jung Choi have contributed equally to this work.

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Yoon, I.K., Choi, Y.J., Chang, B.C. et al. Effects of inflammatory cytokine gene polymorphisms on warfarin maintenance doses in Korean patients with mechanical cardiac valves. Arch. Pharm. Res. 37, 752–759 (2014). https://doi.org/10.1007/s12272-013-0221-4

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