Published Online
on January 23, 2009

A more recent version of this article appeared on February 1, 2009

This Article Full Text (PDF) Data Supplement All Versions of this Article: 2/1/57    most recent CIRCGENETICS.108.801969v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zee, R. Y.L. Articles by Ridker, P. M. Search for Related Content PubMed PubMed Citation Articles by Zee, R. Y.L. Articles by Ridker, P. M. Related Collections Deep vein thrombosis Epidemiology Related Article

Original Article

An Evaluation of Candidate Genes of Inflammation and Thrombosis in Relation to the Risk of Venous Thromboembolism: The Women’s Genome Health Study

Robert Y.L. Zee^1,3; Robert J. Glynn¹; Suzanne Cheng²; Lori Steiner²; Lynda Rose¹ and Paul M. Ridker¹

¹ Brigham and Women's Hospital, Boston, MA;
² Roche Molecular Systems, Inc., Pleasanton, CA

³ E-mail: rzee{at}rics.bwh.harvard.edu

Background—While pathways associated with hemostasis and thrombosis are well-documented to impact upon venous thromboembolism (VTE), whether or not the inflammatory cascade also influences VTE risk is uncertain

Methods and Results—We evaluated 51 polymorphisms from 32 inflammation-related genes (and an additional 19 polymorphisms from 15 thrombosis-related genes) as potential determinants of venous thromboembolism (VTE) in a prospective cohort of 22,413 white women followed over a 10-year period. Hazard ratios for incident VTE according to the different genotypes were assessed by Cox proportional-hazards models. The false discovery rate (FDR) was used for correction for multiple testing with a 0.20 cut-point. During follow-up, 158 idiopathic and 180 secondary VTE events occurred. As anticipated, factor V Leiden (hazard ratio=3.22, 95%CI=1.92-5.40, p<0.0001, FDR=0.004), and the prothrombin mutation (hazard ratio=2.57, 95%CI=1.64-4.02, p<0.0001, FDR=0.004) were both strongly associated with incident idiopathic VTE, as was the rs6046 polymorphism in the factor VII gene (hazard ratio=0.54, 95%CI=0.35-0.86, p=0.008, FDR=0.12). With regard to polymorphism in the inflammatory genes, variation at rs1143634 in the interleukin-1 beta gene was associated with a reduced risk of idiopathic VTE (hazard ratio=0.59, 95%CI=0.44-0.80, p=0.0007, FDR=0.02) while variation at rs1800872 in the interleukin-10 gene was associated with increased risk (hazard ratio=1.42, 95%CI=1.12-1.80, p=0.004, FDR=0.07). By contrast, no significant associations were found for secondary VTE events.

Conclusion—In addition to previously reported polymorphisms associated with hemostasis and thrombosis, these prospective cohort data suggest that genetic variation in IL-1 beta and IL-10 genes may also influence the risk of idiopathic VTE.

Key Words: genetics • risk factors • VTE • candidate genes • polymorphisms

Related Article

An Evaluation of Candidate Genes of Inflammation and Thrombosis in Relation to the Risk of Venous Thromboembolism: The Women’s Genome Health Study

Robert Y.L. Zee, Robert J. Glynn, Suzanne Cheng, Lori Steiner, Lynda Rose, and Paul M Ridker
Circ Cardiovasc Genet 2009 2: 57-62. [Abstract] [Full Text] [PDF]