Genetic risk factors for venous thrombosis in women using combined oral contraceptives: update of the PILGRIM study

Abstract

Identifying women at risk of venous thrombosis (VT) under combined oral contraceptives (COC) is a major public health issue. The aim of this study was to investigate in COC users the impact on disease of genetic polymorphisms recently identified to associate with VT risk in the general population. Nine polymorphisms located on KNG1, F11, F5, F2, PROCR, FGG, TSPAN and SLC44A2 genes were genotyped in a sample of 766 patients and 464 controls as part of the PILGRIM (PILl Genetic Risk Monitoring) study. Cases were women who experienced an episode of documented VT during COC use, while controls were women with no history of VT using COC at the time of inclusion. Among the studied polymorphisms, only F11 rs2289252 was significantly associated with VT. The F11 rs2289252-A allele was associated with a 1.6-fold increased risk of VT (p < 0.0001). Besides, the combination of the rs2289252-A allele with non-O blood group, present in 52% of the cohort, was associated with an odds ratio of 4.00 (2.49–6.47; p < 10−4). The consideration of this genetic risk factor could help to better assess the risk of VT in COC users.