A2.36 Genetic variability and gout

Background and objectives Several recent studies highlighted the importance of special gene loci related to gout and hyperuricaemia. However, it is remarkable that only a minor fraction of hyperuricemic population produces the symptoms of gout. Discussing the pathomechnism of gouty inflammation a potential autoinflammatory explanation has emerged recently. Induced by MSU crystals, the pathologic activity of a multi-protein complex (NLRP3 inflammasome) might be responsible for the increased activation of interleukin 1-beta (IL-1β), a cytokine playing a central role in inflamation. Toll-like receptors (TLR2–4) have also been studied for the stepped-up production of pre- IL-1β, the pre form of the active metabolit. Human erythrocytes express numerous membrane proteins, several of them already identified as homologue proteins to those with specific function in other tissue, such as urate transporters. Our objective was to verify genetical variations, single nucleotid polymorphisms (SNP) leading to hyperuricemia and gout. We also analysed these gene loci coded proteins linked to elevated urate level, using a unique technique (EryTest) based on the presence of special membrane proteins on human erythrocytes. Materials and methods We studied the results of three groups. Patients with gout, control patients with hyperuricemia but with no arthritic event and patients with normal serum uric acid level. Specific monoclonal antibodies and IgG control were used for quantitative flow cytometry to determine proteins. Polymorphism specific and control primers were used for polymerase chain reaction (PCR) detecting SNPs. Results Increased level of CARD8 polymorphism was found in the gout group compared to the two control groups. Decreased ABCG2 protein expression was detected in heterozygous individuals in gouty and hyperuricemic groups compared to normouricemic controls. Conclusions We presume that depending on complex genetic and environmental factors, patients with CARD8 polymorphisms may have increased inflammatory response and those with decreased ABCG2 protein expression may have higher serum urate levels. From the clinical introduction of EryTest, a simple and rapid clinical method in the evaluation of hyperuricemia is expected. To confirm recent results of genetic variability and the clinical use of EryTest, further investigation is planned.