Evaluation of gene expression of liver receptor LRP and factor VIII and their correlation with plasma levels of factor VIII and Von Willebrand factor

• Grant number: 11/05905-6
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2011
• End date: July 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Joyce Maria Annichino-Bizzacchi
• Grantee: Joyce Maria Annichino-Bizzacchi
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Adriana da Silva Santos Duarte ; Erich Vinicius de Paula

Abstract

Venous thromboembolism (VTE) is a multifactorial disease where that needs a dynamic interaction between genetic risk factors and acquired. However, in approximately 30% of patients with VTE does not identify any hereditary or acquired factor, which suggests the presence of additional unknown mechanisms of the disease. Elevated plasma levels of FVIII are an independent, prevalent and dose dependent risk factor for both the first episode of venous thromboembolism and for their recurrence. Studies that included patients with VTE and increased FVIII suggest a pattern of genetic inheritance. The LRP is a hepatic receptor responsible for endocytosis of circulating FVIII. Studies in animal models of transgenic mice deficient in LRP showed that there is an accumulation of FVIII and vWF in plasma in these animals, indicating that LRP deficiency leads to a lower rate of elimination of plasma FVIII. Structural analysis identified the protein regions of both LRP and FVIII that have affinity for each other. The objectives of this project are to evaluate the gene expression of LRP and FVIII and correlate with plasma levels of FVIII and vWF, and also check for mutations or polymorphisms of genes in regions of LRP and FVIII coding regions interaction between both proteins. (AU)