Promoter methylation of coagulation factor VII in patients with traumatic brain injury and its association with intracranial progressive hemorrhagic injury

Abstract

Objective To study the effect of the promoter methylation of coagulation factor VII (FVII) on the coagulation factor VII activity (FVIIa) in traumatic brain injury (TBI) patients, and the correlation between the promoter methylation in FVII and intracranial progressive hemorrhagic injury (PHI). Methods A prospective analysis was conducted on 79 patients with moderate-severe TBI admitted to emergency department from August 2010 to August 2014. The peripheral venous blood samples were collected at admission and then were delivered for measurement of FVIIa. Genomic DNA was isolated from patient blood, and the promoter methylation in FVII (CpG2, CpG3, CpG4, CpG5, and CpG6) were analyzed. According to the level of plasma FVIIa, the patients were divided into FVIIa≥90% group and FVIIa<90% group. Based on the presence of PHI, the patients were divided into PHI group and non-PHI group. The FVII promoter methylation, age, gender, systolic blood pressure, Glasgow Coma Scale (GCS), length of stay and mortality between FVIIa≥90% group and FVIIa<90% group, PHI group and non-PHI group were compared. Results There were no significant differences in age, gender, systolic blood pressure, GCS, LOS, and mortality between FVIIa ≥90% group and FVIIa 0.05). The methylation of CpG3 in FVIIa ≥90% group was less than that in FVIIa 0.05). No significant differences in all of methylation levels of the CpG sites between PHI group and non-PHI group were found (P>0.05). Conclusions The promoter methylation of FVII affects plasma FVIIa concentrations, and higher methylation results in lower FVIIa. The promoter methylation of FVII is not associated with PHI in TBI patients. Key words: Brain injuries; Factor VII; Methylation; Progressive hemorrhagic injury