APOB gene polymorphisms may affect the risk of minor or minimal bleeding complications in patients on warfarin maintaining therapeutic INR

• Published in: European journal of human genetics : EJHG 2019-10, Vol.27 (10), p.1542-1549
• Main Authors: Yee, Jeong, Kim, Woorim, Chang, Byung Chul, Chung, Jee Eun, Lee, Kyung Eun, Gwak, Hye Sun
• Format: Article
• Language: English
• Subjects: Aged; Alleles; APOB gene; Apolipoprotein B-100 - genetics; Apolipoprotein E; Bleeding; Comorbidity; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Heart; Hemorrhage - diagnosis; Hemorrhage - etiology; Humans; International Normalized Ratio; Male; Middle Aged; Polymorphism, Single Nucleotide; ROC Curve; Single-nucleotide polymorphism; Warfarin; Warfarin - adverse effects; Warfarin - therapeutic use
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/s41431-019-0450-1

The purpose of this study was to investigate influence of gene polymorphisms of APOB and APOE on risk of bleeding complications at therapeutic INR, during warfarin treatment in Korean patients with mechanical cardiac valves. The study included 142 patients from the EwhA-Severance Treatment Group (EAST) of Warfarin. A total of 12 SNPs was investigated. Five SNPs of APOB (c.13013G>A, c.1853C>T, c.1594C>T, c.293C>T, and c.7545C>T) and five SNPs of APOE (g.4798T>G, g.6406G>A, g.10413T>C, c.388T>C, and c.526C>T) were selected. In addition to selected SNPs, VKORC1 g.6399C>T, and CYP2C9 c.1075A>C, which were known to have significant effects on warfarin stable doses, were also included in the study. Two SNPs of APOB (c.293C>T and c.1853C>T) were associated with bleeding complications. T allele carriers of c.293C>T had 8.6 times (95% CI 2.9-25.5, p T had 6.4 times (95% CI 2.3-17.9, p T and c.293C>T were 0.771 and 0.802, respectively. Among demographic characteristics, age was the only significant factor. This study revealed that APOB was associated with bleeding complications in patients with warfarin treatment after mechanical cardiac valves.