Copy number variations of the F8 gene are associated with venous thromboembolism

BackgroundVenous thromboembolism (VTE) is a complex disease and several inherited and acquired factors are relevant to its occurrence. Among these, an elevated level of plasma coagulation factor VIII (FVIII) is an established risk factor for VTE; copy number variations (CNVs) have also been discovered to be associated with many diseases.ObjectiveTo explore the proposed association between CNV of the F8 gene and the risk of VTE.MethodsA case–control study including 179 VTE patients and 176 healthy individuals were enrolled in this study. Activity of plasma factor VIII was measured. Genomic DNA was extracted for subsequent quantitative real-time PCR analysis of CNVs of the F8 gene.ResultsPlasma factor VIII levels were significantly higher in VTE patients than in healthy controls (251% vs. 99%, p < 0.01). Copy number of the F8 gene in VTE patients was significantly higher than in healthy controls. (male: p = 6.1 × 10− 14, OR = 12, 95%CI: 6.0–25; female: p = 4.3 × 10− 10, OR = 9.5, 95%CI: 4.5–20). Plasma factor VIII levels in the samples with high copies of the F8 gene were higher than in those individuals with normal copy number (male: p = 0.023; female: p = 0.036).ConclusionsAmplification of the F8 gene copy number seems to enhance factor VIII activity and was associated with VTE.