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

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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

Fingerprint

Cholesterol Ester Transfer Proteins
Hemostatics
Genome-Wide Association Study
Single Nucleotide Polymorphism
Linear Models
Logistic Models
Alleles
Confidence Intervals

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

Cite this

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, 17(9), 1535-1543. https://doi.org/10.1111/jth.14528
Li-Gao, Ruifang ; Mook-Kanamori, Dennis O ; Cannegieter, Suzanne C ; Willems van Dijk, Ko ; Rosendaal, Frits R ; van Hylckama Vlieg, Astrid. / The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis. In: Thrombosis and Haemostasis. 2019 ; Vol. 17, No. 9. pp. 1535-1543.
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title = "The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis",
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.",
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",
author = "Ruifang Li-Gao and Mook-Kanamori, {Dennis O} and Cannegieter, {Suzanne C} and {Willems van Dijk}, Ko and Rosendaal, {Frits R} and {van Hylckama Vlieg}, Astrid",
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pages = "1535--1543",
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Li-Gao, R, Mook-Kanamori, DO, Cannegieter, SC, Willems van Dijk, K, Rosendaal, FR & 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

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.

In: Thrombosis and Haemostasis, Vol. 17, No. 9, 2019, p. 1535-1543.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis

AU - Li-Gao, Ruifang

AU - Mook-Kanamori, Dennis O

AU - Cannegieter, Suzanne C

AU - Willems van Dijk, Ko

AU - Rosendaal, Frits R

AU - van Hylckama Vlieg, Astrid

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - ATHEROSCLEROSIS

KW - DYSLIPOPROTEINEMIA

KW - FACTOR-VII

KW - HIGH-DENSITY-LIPOPROTEIN

KW - Mendelian randomization analysis

KW - PLASMA-LEVELS

KW - RISK

KW - anticoagulants

KW - blood coagulation factors

KW - cholesteryl ester transfer protein

KW - polymorphism

KW - single nucleotide

KW - venous thrombosis

U2 - 10.1111/jth.14528

DO - 10.1111/jth.14528

M3 - Article

VL - 17

SP - 1535

EP - 1543

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 9

ER -