Background: Estrogen and the estrogen receptors alpha (ESR1) and beta (ESR2) play a role in regulating genes, including coagulation and fibrinolysis genes.
Objective: We investigated the association between ESR1 c.454-397T>C and c.454-351A>G and ESR2 1082A>G and 1730A>G polymorphisms and the risk of deep vein thrombosis (DVT), in 134 patients and 134 controls with acquired risk factors for thrombosis associated with estrogen alterations, such as pregnancy, puerperium, oral contraceptives (OC), and hormone replacement therapy (HRT). We also analysed 134 men with DVT. We investigated the relationship of these polymorphisms and the levels of fibrinogen, protein C (PC), protein S (PS), and antithrombin (AT) activity.
Methods: Gene polymorphisms were identified by using PCR and RFLP. Coagulation methods were used to measure PC, PS, and fibrinogen. Chromogenic methods were used to quantify AT.
Results and conclusions: The presence of the AA genotype of the 1730G>A polymorphism (OR=0.18; 95%CI=0.05-0.62) suggests a protective effect for DVT in women using OC. As the GG genotype of the 1730G>A polymorphism is associated with increased PS activity in all control women and women using OC, this suggested that a protective effect must occur by another pathway not related to PS. The AA and AG genotypes of the c.454-351A>G and GG genotype of the 1082G>A polymorphisms are associated with increased fibrinogen concentration in pregnant women. The GG haplotype in the ESR2 gene (P<0.001) was related to factor V Leiden or G20210A mutation in the prothrombin gene, or both, as predictive factors of DVT.