Association of common genetic variations and idiopathic venous thromboembolism. Results from EDITh, a hospital-based case-control study.
Venous thromboembolism (VTE) is a multifactorial disease, caused by interacting environmental and genetic risk factors. Gene-centric genotyping strategy is one of the approaches to explore unexplained associations between risk factors and VTE. It was the objective of this study to evaluate, using a gene-centric genotyping strategy, polymorphisms in genes involved in the following pathways: coagulation cascade process, renin-angiotensin or adrenergic systems, lipid metabolism, platelet aggregation. Allele frequency was compared between 677 cases with idiopathic VTE and their matched controls. After Bonferroni adjustment, four single nucleotide polymorphisms (SNPs) were significantly associated with VTE: Factor XI rs925451 polymorphism, factor XI rs2289252 polymorphism, factor II rs1799963 (G20210A) polymorphism and factor V Leiden rs6025. An additive mode of inheritance fitted best both factor XI polymorphisms. In this hospital-based case-control study, two polymorphisms located on the factor XI gene were significantly associated with VTE. Other newly investigated polymorphisms with potentially false negatives may warrant further analyses.
Delluc
Aurélien
A
Université Européeenne de Bretagne, Université de Brest, Brest, France.
Gourhant
Lénaïck
L
Lacut
Karine
K
Mercier
Bernard
B
Audrezet
Marie-Pierre
MP
Nowak
Emmanuel
E
Oger
Emmanuel
E
Leroyer
Christophe
C
Mottier
Dominique
D
Le Gal
Grégoire
G
Couturaud
Francis
F
D000368:Aged; D001777:Blood Coagulation / Q000235:genetics; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics; D005172:Factor XI / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006761:Hospitals; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011516:Prothrombin / Q000235:genetics*; D011941:Receptors, Adrenergic / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics; D054556:Venous Thromboembolism / Q000235:genetics* / Q000503:physiopathology
D011941:Receptors, Adrenergic; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D005172:Factor XI