A Follow-Up Study of a Genome-wide Association Scan Identifies a Susceptibility Locus for Venous Thrombosis on Chromosome 6p24.1

被引：56

作者：

Morange, Pierre-Emmanuel ^{[1
]}

Bezemer, Irene ^{[2
,3
]}

Saut, Noemie ^{[1
]}

Bare, Lance ^{[4
]}

Burgos, Gwenaelle ^{[1
]}

Brocheton, Jessy ^{[5
,13
]}

Durand, Herve ^{[5
,13
]}

Biron-Andreani, Christine ^{[6
]}

Schved, Jean-Francois ^{[6
]}

Pernod, Gilles ^{[7
]}

Galan, Pilar ^{[8
,14
]}

Drouet, Ludovic ^{[5
,13
]}

Zelenika, Diana ^{[9
]}

Germain, Marine ^{[5
,13
]}

Nicaud, Viviane ^{[5
,13
]}

Heath, Simon ^{[9
]}

Ninio, Ewa ^{[5
,13
]}

Delluc, Aurelien ^{[10
,12
]}

Muenzel, Thomas ^{[11
]}

Zeller, Tanja ^{[11
]}

Brand-Herrmann, Stefan-Martin ^{[15
]}

Alessi, Marie-Christine ^{[1
]}

Tiret, Laurence ^{[5
,13
]}

Lathrop, Mark ^{[9
]}

Cambien, Francois ^{[5
,13
]}

Blankenberg, Stefan ^{[11
]}

Emmerich, Joseph ^{[16
]}

Tregouet, David-Alexandre ^{[5
,13
]}

Rosendaal, Frits R. ^{[2
,3
]}

机构：

[1] Univ Mediterranee, INSERM, UMR S 626, F-13385 Marseille, France

[2] Leiden Univ, Dept Thrombosis & Hemostasis, Dept Clin Epidemiol, Med Ctr, NL-2300 MC Leiden, Netherlands

[3] Leiden Univ, Einthoven Lab Expt Vasc Med, Med Ctr, NL-2300 MC Leiden, Netherlands

[4] Celera, Alameda, CA 94502 USA

[5] INSERM, UMRS 937, F-75013 Paris, France

[6] CHU Montpellier, Hematol Lab, F-34295 Montpellier, France

[7] CHU Grenoble, Serv Med Vasc, F-38043 Grenoble, France

[8] INSERM, UMR S U872, F-75270 Paris, France

[9] Ctr Natl Genotypage, Commissariat Energie Atom, Inst Genom, F-91057 Evry, France

[10] Univ Brest, EA3878, INSERM, IFR 148, F-29609 Brest, France

[11] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin, Univ Med, D-55131 Mainz, Germany

[12] Brest Univ Hosp, Dept Internal Med & Chest Dis, F-29609 Brest, France

[13] Univ Paris 06, F-75013 Paris, France

[14] Fac Med Rene Descartes, Dept Sante Publ & Informat Med, F-75270 Paris, France

[15] Univ Munster, Leibniz Inst Arteriosclerosis Res, Dept Mol Genet Cardiovasc Dis, D-48149 Munster, Germany

[16] Univ Paris 05, INSERM, U765, Med Vasc HTA,Hop Europeen Georges Pompidou, F-75908 Paris, France

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2010年 / 86卷 / 04期

关键词：

LINKING INFLAMMATION; PROTEIN; RISK;

D O I：

10.1016/j.ajhg.2010.02.011

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：592 / 595

页数：4

共 15 条

[1] The CD40/CD40 Ligand System Linking Inflammation With Atherothrombosis [J].

Antoniades, Charalambos ;

Bakogiannis, Constantinos ;

Tousoulis, Dimitris ;

Antonopoulos, Alexios S. ;

Stefanadis, Christodoulos .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2009, 54 (08) :669-677

[2] A LARGE PROTEIN CONTAINING ZINC FINGER DOMAINS BINDS TO RELATED SEQUENCE ELEMENTS IN THE ENHANCERS OF THE CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX AND KAPPA-IMMUNOGLOBULIN GENES [J].

BALDWIN, AS ;

LECLAIR, KP ;

SINGH, H ;

SHARP, PA .

MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (04) :1406-1414

[3] Malignancies, prothrombotic mutations, and the risk of venous thrombosis [J].

Blom, JW ;

Doggen, CJM ;

Osanto, S ;

Rosendaal, FR .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2005, 293 (06) :715-722

[4] Matlnspector and beyond: promoter analysis based on transcription factor binding sites [J].

Cartharius, K ;

Frech, K ;

Grote, K ;

Klocke, B ;

Haltmeier, M ;

Klingenhoff, A ;

Frisch, M ;

Bayerlein, M ;

Werner, T .

BIOINFORMATICS, 2005, 21 (13) :2933-2942

[5] Inflammation and thrombosis [J].

Esmon, CT .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2003, 1 (07) :1343-1348

[6] A DNA-BINDING PROTEIN CONTAINING 2 WIDELY SEPARATED ZINC FINGER MOTIFS THAT RECOGNIZE THE SAME DNA-SEQUENCE [J].

FAN, CM ;

MANIATIS, T .

GENES & DEVELOPMENT, 1990, 4 (01) :29-42

[7] SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap [J].

Johnson, Andrew D. ;

Handsaker, Robert E. ;

Pulit, Sara L. ;

Nizzari, Marcia M. ;

O'Donnell, Christopher J. ;

de Bakker, Paul I. W. .

BIOINFORMATICS, 2008, 24 (24) :2938-2939

[8] HUMAN-GENETICS - BAD BLOOD BY MUTATION [J].

MAJERUS, PW .

NATURE, 1994, 369 (6475) :14-15

[9] NF-κB inhibitors impair platelet activation responses [J].

Malaver, E. ;

Romaniuk, M. A. ;

D'Atri, L. P. ;

Pozner, R. G. ;

Negrotto, S. ;

Benzadon, R. ;

Schattner, M. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2009, 7 (08) :1333-1343

[10] Deciphering the molecular basis of venous thromboembolism: where are we and where should we go? [J].

Morange, Pierre-Emmanuel ;

Tregouet, David-Alexandre .

BRITISH JOURNAL OF HAEMATOLOGY, 2010, 148 (04) :495-506

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