A follow-up study of a genome-wide association scan identifies a susceptibility locus for venous thrombosis on chromosome 6p24.1.
To identify genetic susceptibility factors conferring increased risk of venous thrombosis (VT), we conducted a multistage study, following results of a previously published GWAS that failed to detect loci for developing VT. Using a collection of 5862 cases with VT and 7112 healthy controls, we identified the HIVEP1 locus on chromosome 6p24.1 as a susceptibility locus for VT. Indeed, the HIVEP1 rs169713C allele was associated with an increased risk for VT, with an odds ratio of 1.20 (95% confidence interval 1.13-1.27, p = 2.86 x 10(-9)). HIVEP1 codes for a protein that participates in the transcriptional regulation of inflammatory target genes by binding specific DNA sequences in their promoter and enhancer regions. The current results provide the identification of a locus involved in VT susceptibility that lies outside the traditional coagulation/fibrinolysis pathway.
Morange
Pierre-Emmanuel
PE
INSERM, UMR_S 626, Université de la Méditerranée, Marseille, F-13385 France. pierre.morange@ap-hm.fr
Bezemer
Irene
I
Saut
Noémie
N
Bare
Lance
L
Burgos
Gwenaelle
G
Brocheton
Jessy
J
Durand
Hervé
H
Biron-Andreani
Christine
C
Schved
Jean-Francois
JF
Pernod
Gilles
G
Galan
Pilar
P
Drouet
Ludovic
L
Zelenika
Diana
D
Germain
Marine
M
Nicaud
Viviane
V
Heath
Simon
S
Ninio
Ewa
E
Delluc
Aurélien
A
Münzel
Thomas
T
Zeller
Tanja
T
Brand-Herrmann
Stefan-Martin
SM
Alessi
Marie-Christine
MC
Tiret
Laurence
L
Lathrop
Mark
M
Cambien
François
F
Blankenberg
Stefan
S
Emmerich
Joseph
J
Trégouët
David-Alexandre
DA
Rosendaal
Frits R
FR
D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics*
D004268:DNA-Binding Proteins; C063232:HIVEP1 protein, human; D014157:Transcription Factors