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The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis
Li-Gao,Ruifang Mook-Kanamori,Dennis O Cannegieter,Suzanne C Willems van Dijk,Ko Rosendaal,Frits R van Hylckama Vlieg,Astrid
Li-Gao,Ruifang
Mook-Kanamori,Dennis O
Cannegieter,Suzanne C
Willems van Dijk,Ko
Rosendaal,Frits R
van Hylckama Vlieg,Astrid
Abstract
Background: Cholesteryl ester transfer protein (CETP) plays an important role in lipoprotein metabolism. Previous studies have suggested that the CETP TaqI B1/B2 allele is associated with the risk of venous thrombosis (VT). Aim: To investigate the associations between genetically determined CETP concentrations and 22 hemostatic factors in healthy individuals, and the risk of a first VT event, in a large VT case-control study. Methods: Analyses were performed in the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) case-control study. CETP unweighted/weighted genetic risk scores (GRSs) were derived from three single-nucleotide polymorphisms that were identified from a recent genome-wide association study on serum CETP concentrations. The associations between CETP GRSs and 22 hemostatic factors (procoagulant/anticoagulant and fibrinolytic factors) were assessed by linear regression from an additive model in controls (n = 2813). The associations between CETP GRSs and the risk of a first VT were assessed by logistic regression analyses in 3950 VT cases and 4765 controls. Results: In the controls (median age, 49 years; 53% women), both unweighted and weighted GRSs showed that factor VII activity was negatively associated with the genetically determined CETP concentration (weighted GRS β -3.08 IU/dL per μg/mL genetically determined CETP, 95% confidence interval -5.73 to -0.42). No association was observed with the risk of a first VT. Conclusions: Genetically determined CETP concentrations only showed a weak negative association with factor VII activity. However, this did not lead to an association with the risk of a first VT.
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Date
2019
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Research Projects
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Keywords
ATHEROSCLEROSIS, DYSLIPOPROTEINEMIA, FACTOR-VII, HIGH-DENSITY-LIPOPROTEIN, Mendelian randomization analysis, PLASMA-LEVELS, RISK, anticoagulants, blood coagulation factors, cholesteryl ester transfer protein, polymorphism, single nucleotide, venous thrombosis
Citation
Li-Gao, R, Mook-Kanamori, D O, Cannegieter, S C, Willems van Dijk, K, Rosendaal, F R & van Hylckama Vlieg, A 2019, 'The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis', Thrombosis and Haemostasis, vol. 17, no. 9, pp. 1535-1543. https://doi.org/10.1111/jth.14528