Association between HNF4A mutations and bleeding complications in patients with stable international normalized ratio

This study aimed to determine the association between hepatocyte nuclear factor 4 alpha (HNF4A) polymorphisms and bleeding complications in patients on warfarin with international normalized ratios between 2.0 and 3.0 after cardiac valve replacement.

Nineteen single nucleotide polymorphisms of HNF4A in addition to VKORC1 rs9934438 and CYP2C9 rs1057910 were analyzed. Univariate and multivariate analyses were conducted to evaluate associations between genetic polymorphisms and bleeding risk. Attributable risk and number needed to genotype (NNG) were calculated to assess clinical value of genotyping.

Of 142 patients, 21 experienced bleeding complications. Multivariate logistic regression analysis was conducted using factors with P <0.1 in univariate analysis. Multivariate analysis showed that patients with the CC genotype of rs6130615 had an 8.4-fold increased risk of bleeding, compared with patients with the T allele. Attributable risk and NNG were 88.1% and 32.2, respectively. Patients with the TT genotype of rs3212191 had a 3.8-fold increased risk of bleeding, compared with C allele carriers, while patients with variant-type homozygotes for rs1884613 showed an 8.7-fold higher bleeding complication than C allele carriers. The attributable risk/NNG of rs3212191 and rs1884613 were 73.4%/17.6 and 88.5%/22.8, respectively. Among comorbidities, atrial fibrillation was the only significant risk factor for bleeding complications.

Bleeding complications during warfarin therapy in patients with mechanical heart valves were associated with HNF4A polymorphisms and atrial fibrillation.