IP: Dr. Juan García Puig

Resumen del proyecto: Background: Gout is a syndrome of unknown aetiology in the vast majority of the patients (primary gout, 95%) due to tissue deposition of the sodium salt of uric acid (crystals composed of monosodium urate). Gout incidence has increased in the last 20 years due to modern life style in industrialized societies and to the increased incidence of the metabolic syndrome. Among primary gout patients over 90% show a reduced renal excretion of urate for their increased serum urate concentrations. This means that in the majority the metabolic uric acid disorder is due to a kidney dysfunction for urate excretion. URAT1 transporter is responsible for tubular urate reabsorption in the proximal renal tubule and modulates circulating urate levels. We postulate that urate underexcretion in gout patients may be related to a defect in the URAT1 transporter. Objectives: Primary objective: Implication of the transporter URAT1 in the pathogenesis of gout due to renal urate underexcretion. The following secondary objectives will be covered: Objective 1: We will obtain a DNA bank from patients with gout and uric acid underexcretion. Objective 2: Molecular analysis of the URAT 1 gene in patients with gout and uric acid underexcretion. Objective 3: Relationship between URAT 1 gene polymorphisms and serum urate concentrations and/or renal urate excretion.
Methodology: Objective 1: venous blood will be obtained with EDTA for DNA extraction in patients fulfilling all the inclusion and exclusion criteria, and from a control group. Objective 2: amplification and sequencing the URAT1 gene 10 exons and the intronic sequences from the genomic DNA, by the polymerase chain reaction (PCR) and automatic sequencing; Objective 3: URAT1 gene polymorphisms will be analyzed by fluorescence melting curve analysis in a LightCycler 480 (Roche) System.

Entidad financiadora: Instituto de Salud Carlos III