Investigation of Genetic Disturbances in Oxygen Sensing and Erythropoietin Signaling Pathways in Cases of Idiopathic Erythrocytosis

Author(s)

Dinardo, Carla Luana ; Junior Lima Santos, Paulo Caleb ; Schettert, Isolmar Tadeu ; Gadi Soares, Renata Alonso ; Krieger, Jose Eduardo ; Pereira, Alexandre Costa

• Document type: Journal article
• Source: GENETICS RESEARCH INTERNATIONAL; v. 2013, p. 4-pg., 2013-01-01.

Abstract

Background. Idiopathic erythrocytosis is the termreserved for cases with unexplained origins of abnormally increased hemoglobin after initial investigation. Extensive molecular investigation of genes associated with oxygen sensing and erythropoietin signaling pathways, in those cases, usually involves sequencing all of their exons and it may be time consuming. Aim. To performa strategy for molecular investigation of patients with idiopathic erythrocytosis regarding oxygen sensing and erythropoietin signaling pathways. Methods. Samples of patients with idiopathic erythrocytosis were evaluated for the EPOR, VHL, PHD2, and HIF-2 alpha genes using bidirectional sequencing of their hotspots. Results. One case was associated with HIF-2 alpha mutation. Sequencing did not identify any pathogenic mutation in 4 of 5 cases studied in any of the studied genes. Three known nonpathogenic polymorphisms were found (VHL p. P25L, rs35460768; HIF-2 alpha p. N636N, rs35606117; HIF-2 alpha p. P579P, rs184760160). Conclusion. Extensive molecular investigation of cases considered as idiopathic erythrocytosis does not frequently change the treatment of the patient. However, we propose a complementarymolecular investigation of those cases comprising genes associated with erythrocytosis phenotype to meet both academic and genetic counseling purposes. (AU)

• FAPESP's process: 10/17881-1 - Pharmacogenetic analysis using warfarin drug and in the Brazilian general population
• Grantee: Renata Alonso Gadi Soares
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/20614-3 - Pharmacogenetic analyses for cardiovascular drugs focusing on implementation
• Grantee: Paulo Caleb Júnior de Lima Santos
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 13/09295-3 - Pharmacogenetic of cardiovascular system drugs focusing on implementation
• Grantee: Paulo Caleb Júnior de Lima Santos
• Support Opportunities: Research Grants - Young Investigators Grants