TY - JOUR
T1 - Effects of Polymorphisms in Myc-Related Genes on Bleeding Complications in Patients with Stable Warfarin Responses
AU - Yee, Jeong
AU - Kim, Woorim
AU - Chang, Byung Chul
AU - Chung, Jee Eun
AU - Lee, Kyung Eun
AU - Gwak, Hye Sun
N1 - Publisher Copyright:
© 2019 Jeong Yee et al.
PY - 2019
Y1 - 2019
N2 - Objectives. This study aimed to identify the possible effects of Myc and 8q24 polymorphisms on bleeding complications in patients who maintained international normalized ratio (INR) of 2.0-3.0 with warfarin therapy after cardiac valve replacement. Methods. Twenty-five single nucleotide polymorphisms were analyzed, including VKORC1, CYP2C9, Myc, and 8q24. Univariate and multivariate analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding complications. Attributable risk and the number needed to genotype (NNG) were also calculated to evaluate the potential clinical value of genotyping. Results. We included 142 patients, among whom 21 experienced bleeding complications. Multivariate models showed that patients carrying the CC genotype of rs6983561 and the A allele of rs13281615 at 8q24 had 27.6- and 10.0-fold higher bleeding complications, compared with patients with the A allele and the GG genotype, respectively. For rs6983561, the attributable risk and NNG were 96.4% and 36.8, respectively, whereas, for rs13281615, the attributable risk and NNG were 90.0% and 8.3, respectively. Atrial fibrillation was associated with a 5.5-fold increased risk of bleeding complications. The AUROC value was 0.761 (95% CI 0.659-0.863, p<0.001), and the Hosmer-Lemeshow test showed that the fitness of the multivariate analysis model was satisfactory (χ 2=0.846; 3 degrees of freedom; p=0.838). Conclusions. Bleeding complications during warfarin therapy were associated with 8q24 polymorphisms and atrial fibrillation in patients with mechanical heart valves.
AB - Objectives. This study aimed to identify the possible effects of Myc and 8q24 polymorphisms on bleeding complications in patients who maintained international normalized ratio (INR) of 2.0-3.0 with warfarin therapy after cardiac valve replacement. Methods. Twenty-five single nucleotide polymorphisms were analyzed, including VKORC1, CYP2C9, Myc, and 8q24. Univariate and multivariate analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding complications. Attributable risk and the number needed to genotype (NNG) were also calculated to evaluate the potential clinical value of genotyping. Results. We included 142 patients, among whom 21 experienced bleeding complications. Multivariate models showed that patients carrying the CC genotype of rs6983561 and the A allele of rs13281615 at 8q24 had 27.6- and 10.0-fold higher bleeding complications, compared with patients with the A allele and the GG genotype, respectively. For rs6983561, the attributable risk and NNG were 96.4% and 36.8, respectively, whereas, for rs13281615, the attributable risk and NNG were 90.0% and 8.3, respectively. Atrial fibrillation was associated with a 5.5-fold increased risk of bleeding complications. The AUROC value was 0.761 (95% CI 0.659-0.863, p<0.001), and the Hosmer-Lemeshow test showed that the fitness of the multivariate analysis model was satisfactory (χ 2=0.846; 3 degrees of freedom; p=0.838). Conclusions. Bleeding complications during warfarin therapy were associated with 8q24 polymorphisms and atrial fibrillation in patients with mechanical heart valves.
UR - http://www.scopus.com/inward/record.url?scp=85066026978&partnerID=8YFLogxK
U2 - 10.1155/2019/1813747
DO - 10.1155/2019/1813747
M3 - Article
C2 - 31772606
AN - SCOPUS:85066026978
SN - 1755-5914
VL - 2019
JO - Cardiovascular Therapeutics
JF - Cardiovascular Therapeutics
M1 - 1813747
ER -