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The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis
Author(s) -
LiGao Ruifang,
MookKanamori Dennis O.,
Cannegieter Suzanne C.,
Willems van Dijk Ko,
Rosendaal Frits R.,
van Hylckama Vlieg Astrid
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14528
Subject(s) - cholesterylester transfer protein , medicine , risk factor , confidence interval , venous thrombosis , factor vii , case control study , single nucleotide polymorphism , endocrinology , coagulation , genetics , thrombosis , biology , cholesterol , genotype , lipoprotein , gene
Background Cholesteryl ester transfer protein ( CETP ) plays an important role in lipoprotein metabolism. Previous studies have suggested that the CETP Taq I 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 ( GRS s) 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 GRS s 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 GRS s 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 GRS s 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 .