Asymptomatic hyperuricemia and gout: genetic relationships

Introduction. Uric acid is the end product of purine base metabolism, and elevated serum levels are defined as hyperuricemia. Although hyperuricemia is a prerequisite for the onset of gout, not all patients with elevated uric acid have a debut disease. To date, no specific genetic markers have been identified that can reliably predict the development of gout in patients with asymptomatic hyperuricemia or the progression of the disease to a chronic tophaceous form. The aim of the study was to evaluate genetic relationships in asymptomatic hyperuricemia and gout. Methods. The study included 61 patients with gout and 69 patients with osteoarthritis and asymptomatic hyperuricemia. Polymorphisms of regulatory regions of the genes were investigated: TNFA-238 A/G, TNFA-308 A/G, TNFA-863 C/A, IL1B-31 C/T, IL6-174 C/G, IL8-251 A/T, TIr4 Asp299Gly, TIr4 Thr399ILI and ABCG2 C421A. Results. The frequency of IL1B-31 TT, IL6-174 GG genotypes differed significantly between patients with gout and asymptomatic hyperuricemia (OR=2.4, 95% CI 1.15-5.02, p=0.027 and OR=0.35, 95% CI 0.16-0.76, p=0.009, respectively). In the analysis of complex genotypes, 132 statistically significant positive-associated variants with the development of gout and 96 statistically significant protective variants in various combinations were identified. For women, 137 statistically significant positive-associated variants with the presence of gout in various combinations were identified. Conclusions. The data obtained strongly suggest that the use of complex genetic factors whose products are involved in the pathological process has great informativeness in the identification of protective and resistant markers of gout development and can be used in screening studies.