The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis.
Adolescent
Adult
Aged
Alleles
Blood Proteins
/ analysis
Case-Control Studies
Cholesterol Ester Transfer Proteins
/ genetics
Factor VII
/ analysis
Female
Genetic Association Studies
Hemostasis
Humans
Male
Middle Aged
Netherlands
/ epidemiology
Polymorphism, Single Nucleotide
Pulmonary Embolism
/ blood
Risk
Venous Thrombosis
/ blood
Young Adult
Mendelian randomization analysis
anticoagulants
blood coagulation factors
cholesteryl ester transfer protein
polymorphism
single nucleotide
venous thrombosis
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
13
02
2019
revised:
24
05
2019
accepted:
29
05
2019
pubmed:
31
5
2019
medline:
21
8
2020
entrez:
1
6
2019
Statut:
ppublish
Résumé
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). 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31148376
doi: 10.1111/jth.14528
pii: S1538-7836(22)14145-0
doi:
Substances chimiques
Blood Proteins
0
CETP protein, human
0
Cholesterol Ester Transfer Proteins
0
Factor VII
9001-25-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1535-1543Subventions
Organisme : The Netherlands Heart Foundation
ID : 98.113
Pays : International
Organisme : Dutch Cancer Foundation
ID : 99/1992
Pays : International
Organisme : The Netherlands Organization for Scientific Research
ID : 912-03-033 2003
Pays : International
Informations de copyright
© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.
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