The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis

Ruifang Li-Gao*, Dennis O Mook-Kanamori, Suzanne C Cannegieter, Ko Willems van Dijk, Frits R Rosendaal, Astrid van Hylckama Vlieg

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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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.

Original languageEnglish
Pages (from-to)1535-1543
JournalThrombosis and Haemostasis
Volume17
Issue number9
DOIs
Publication statusPublished - 2019

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

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