Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk

Arteriosclerosis, Thrombosis, and Vascular Biology
Sekar KathiresanChristopher J O'Donnell

Abstract

We undertook a linkage disequilibrium (LD)-based genetic approach to investigate the hypothesis that common sequence variants in 5 thrombosis genes influence plasma hemostatic protein levels or risk of cardiovascular disease (CVD). In a reference panel, we characterized LD structure at the fibrinogen gene cluster (fibrinogen-beta[FGB], FGA, and FGG), factor VII (F7), and tissue plasminogen activator (PLAT) loci. Forty-one tag single nucleotide polymorphisms (SNPs) were genotyped in 1811 unrelated Framingham Heart Study participants. There were significant associations of 9 FGB SNPs with fibrinogen level (minimum P=0.002) and of 7 F7 SNPs and factor VII level (minimum P<0.0001). SNPs at the PLAT locus were not associated with PLAT level. In stepwise analysis, a single FGB variant explained 1% of the residual variance in fibrinogen level, and 2 F7 SNPs together explained 10% of the residual variance in factor VII level. Two PLAT haplotypes were associated with CVD (multivariable-adjusted global P=0.0004). A comprehensive survey of common sequence variation demonstrates that cis-regulatory SNPs explain a modest proportion of the residual variance in circulating fibrinogen and factor VII level and PLAT haplotypes increase the risk ...Continue Reading

References

Sep 1, 1979·American Journal of Epidemiology·W B KannelW P Castelli
Apr 14, 1994·The New England Journal of Medicine·M E MarenbergU de Faire
Jan 19, 1996·The Journal of Biological Chemistry·E S PollakK A High
Jun 15, 2000·The New England Journal of Medicine·H P Kohler, P J Grant
Feb 24, 2001·Lancet·M de LangeP J Grant
May 11, 2001·Nature·D E ReichE S Lander
Oct 5, 2001·Nature Genetics·G C JohnsonJ A Todd
Jan 16, 2002·American Journal of Human Genetics·Daniel J SchaidGregory A Poland
May 25, 2002·Science·Stacey B GabrielDavid Altshuler
Mar 18, 2004·Journal of the National Cancer Institute·Sholom WacholderNathaniel Rothman
Mar 20, 2004·Stroke; a Journal of Cerebral Circulation·Jim JannesSimon A Koblar
Mar 27, 2004·Thrombosis and Haemostasis·Guido A RositoGeoffrey H Tofler
Mar 31, 2004·Nature Genetics·Matthew L FreedmanDavid Altshuler
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
Nov 16, 2004·Nature Genetics·John P A IoannidisThomas A Trikalinos
Oct 29, 2005·Nature·UNKNOWN International HapMap Consortium

❮ Previous
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Citations

Dec 12, 2012·Journal of Thrombosis and Thrombolysis·Pia LarssonSverker Jern
Jan 13, 2009·American Journal of Respiratory and Critical Care Medicine·Annette PetersUNKNOWN AIRGENE Study Group
Feb 24, 2007·Blood·Victoria J ChristiansenPatrick A McKee
Aug 14, 2008·BMC Medical Genetics·Lyle G BestShelley Cole
Apr 12, 2011·Lipids in Health and Disease·Juan Criado-GarcíaUNKNOWN Spanish Group for the Study of Familiar Hypercholesterolemia
Nov 23, 2012·Journal of Translational Medicine·Rossella TomaiuoloMarcello Ciaccio
Mar 12, 2008·Journal of Thrombosis and Haemostasis : JTH·K JoodC Jern
Mar 1, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Jie HuangUNKNOWN CHARGE Consortium Hemostatic Factor Working Group
Nov 17, 2009·British Journal of Haematology·Pierre-Emmanuel Morange, David-Alexandre Tregouet
Jul 16, 2010·Journal of Thrombosis and Haemostasis : JTH·P M MannucciD Ardissino
Nov 26, 2008·Acta Anaesthesiologica Scandinavica·B OsterlundB Biber

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