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TGF-β1 polymorphism increases the risk of bleeding complications in patients on oral anticoagulant after cardiac valve replacement

Title
TGF-β1 polymorphism increases the risk of bleeding complications in patients on oral anticoagulant after cardiac valve replacement
Authors
Kim W.Yee J.Chang B.C.Chung J.E.Lee K.E.Gwak H.S.
Ewha Authors
곽혜선
SCOPUS Author ID
곽혜선scopus
Issue Date
2021
Journal Title
Heart and Vessels
ISSN
0910-8327JCR Link
Citation
Heart and Vessels vol. 36, no. 12, pp. 1885 - 1891
Keywords
BleedingMechanical heart valvePolymorphismTGF-β1Warfarin
Publisher
Springer Japan
Indexed
SCIE; SCOPUS scopus
Document Type
Article
Abstract
Although an elevated INR is highly associated with an increased risk of warfarin-associated bleeding, it has been reported that some patients also experience bleeding complications at therapeutic INRs. TGF-β1 polymorphisms has been reported to cause vascular malformations, resulting in bleeding complications, but there are few published genetic studies regarding bleeding complications in patients on warfarin therapy. This study aimed to determine if there is an association between transforming growth factor beta-1 (TGF-β1) polymorphisms and bleeding complications in patients who maintain international normalized ratios (INRs) of 2.0–3.0 with warfarin therapy after cardiac valve replacement. Eleven single nucleotide polymorphis (SNPs) of TGF-β1 (rs1800469, rs2241718, rs4803455, rs2241717, rs2241716, rs2241715, rs2241714, rs11083616, rs2317130, rs747857, and rs1982073) were analyzed. Univariate and multivariable analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding risk. Attributable risk and the number needed to genotype (NNG) were calculated to identify the potential clinical value of genotyping. A discrimination of model was assessed via an analysis of the area under the receiver operating curve (AUROC). To test the model’s goodness of fit, a Hosmer–Lemeshow test was performed. Of 142 patients, 21 experienced bleeding complications. Among analyzed single nucleotide polymorphis (SNPs) of TGF-β1 (rs1800469, rs2241718, rs4803455, rs2241717, rs2241716, rs2241715, rs2241714, rs11083616, rs2317130, rs747857, and rs1982073), AA genotype carriers in rs2241718 had about 5.5 times more bleeding complications than those with the G allele after adjusting for other confounders. The attributable risk and NNG for rs2241718 were 81.9% and 57.8, respectively. The presence of atrial fibrillation and myocardial infarction increased bleeding complications 3.9- and 9.8-fold, compared with those without atrial fibrillation and myocardial infarction, respectively. Bleeding complications during warfarin therapy in patients with mechanical heart valves were associated with TGF-β1 polymorphisms as well as atrial fibrillation and myocardial infarction. © 2021, Springer Japan KK, part of Springer Nature.
DOI
10.1007/s00380-021-01867-2
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약학대학 > 약학과 > Journal papers
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