title: Association between estrogen receptor alpha and beta gene polymorphisms and deep vein thrombosis.
abstract: 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.
  
  
  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.
authors.affiliation: Hematology-Hemotherapy Center, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. joyce@unicamp.br
authors.forename: Aline Morandi
authors.initials: AM
authors.lastname: Aléssio
authors.forename: Nelci Fenalti
authors.initials: NF
authors.lastname: Höehr
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Siqueira
authors.forename: Margareth Castro
authors.initials: MC
authors.lastname: Ozelo
authors.forename: Antônio
authors.initials: A
authors.lastname: de Pádua Mansur
authors.forename: Joyce Maria
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000991:Antithrombins / Q000096:biosynthesis; D001777:Blood Coagulation; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011486:Protein C / Q000096:biosynthesis; D017293:Protein S / Q000096:biosynthesis; D020246:Venous Thrombosis / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D000991:Antithrombins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011486:Protein C; D017293:Protein S; D005340:Fibrinogen