Gene variants associated with deep vein thrombosis

Abstract

Context: The genetic causes of deep vein thrombosis (DVT) are not fully understood. Objective: To identify single-nucleotide polymorphisms (SNPs) associated with DVT. Design, Setting, and Patients: We used 3 case-control studies of first DVT. A total of 19 682 gene-centric SNPs were genotyped in 443 cases and 453 controls from the Leiden Thrombophilia Study (LETS, 1988-1992). Twelve hundred six SNPs associated with DVT were reinvestigated in the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (MEGA-1, 1999-2004) in a subset of 1398 cases and 1757 controls. Nine SNPs associated with DVT in both LETS and MEGA-1 were investigated a third time in 1314 cases and 2877 controls from MEGA-2, a second subset of MEGA. Additional SNPs close to one SNP in CYP4V2 were genotyped in LETS and MEGA-1. Main Outcome Measure: Odds ratios (ORs) for DVT were estimated by logistic regression. False discovery rates served to investigate the effect of multiple hypothesis testing. Results: Of 9 SNPs genotyped in MEGA-2, 3 were strongly associated with DVT (P