Genetic and biochemical markers for diagnosis, prognosis and treatment of age-related macular degeneration

• Grant number: 12/19334-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2013
• End date: April 30, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Dorotéia Rossi Silva Souza
• Grantee: Dorotéia Rossi Silva Souza
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil
• Associated researchers: Rubens Camargo Siqueira

Abstract

Age-related macular degeneration (AMD) is a complex disorder of multifactorial eye that affects the elderly, being the third leading cause of blindness worldwide. AMD results in progressive and irreversible loss of central vision that affects the macula of the eye and involves the retinal pigment epithelium (RPE), Bruch's membrane (BM), coriocapilares. Genetic risk factors have been associated with the disease, including high expression of the gene variants and polymorphisms of vascular endothelial growth factor (VEGF), apolipoprotein E4 (APOE*4), and a member of the A subfamily of ABC transporters adenosine triphosphate-binding cassette (ABCA4). Objectives- Evaluate the influence of polymorphisms VEGF-C936T, APOE-HhaI and ABCA4 in patients with age-related macular degeneration (ARMD); evaluate the gene expression of VEGF, ABCA4, and APOE in peripheral blood and intraocular tissue of patients with AMD (exudative form); verify the existence of a correlation between the expression of the different genes proposed for each group, separately; correlate the risk genotypes with response to drug treatment in exudative form of the disease and to analyze the association between AMD, genetic variants for VEGF-C936T, APOE-Hha-I and ABCA4 variants and for lifestyle and personal history, including sex, age, diabetes mellitus, hypertension and dyslipidemia. Methods- 354 individuals will be selected, regardless of gender, ethnicity and age, in three groups. Group 1 (G1) - 118 individuals diagnosed with age-related macular degeneration in dry form, Group 2 (G2) -118 individuals with macular degeneration related to age as exudative and Group 3 (G3) - 118 individuals with macular degeneration not related with age. Nucleic acids (DNA and RNA) are extracted from peripheral blood and glass, respectively. Conventional PCR will be performed in real time for analysis of samples. The biochemical analysis will be carried out using enzyme immunoassay (EIA) and by ELISA. Statistical analysis will include the Fisher exact test, multivariate regression, with significance level P <0.05. (AU)