BACKGROUND: Venous 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. OBJECTIVE: To explore the proposed association between CNV of the F8 gene and the risk of VTE. METHODS: A 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. RESULTS: Plasma 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). CONCLUSIONS: Amplification of the F8 gene copy number seems to enhance factor VIII activity and was associated with VTE.
BACKGROUND:Venous 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. OBJECTIVE: To explore the proposed association between CNV of the F8 gene and the risk of VTE. METHODS: A case-control study including 179 VTEpatients 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. RESULTS: Plasma factor VIII levels were significantly higher in VTEpatients than in healthy controls (251% vs. 99%, p<0.01). Copy number of the F8 gene in VTEpatients 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). CONCLUSIONS: Amplification of the F8 gene copy number seems to enhance factor VIII activity and was associated with VTE.
Authors: David N Cooper; Michael Krawczak; Constantin Polychronakos; Chris Tyler-Smith; Hildegard Kehrer-Sawatzki Journal: Hum Genet Date: 2013-07-03 Impact factor: 4.132