Career situation of first and presenting author Student for a master or a PhD.
Introduction Serum uric acid concentration is significantly influenced by urate transporters, such as ABCG2 (encoded by ABCG2 gene), GLUT9 (SLC2A9 gene) and URAT1 (SLC22A12 gene). The main function of ABCG2 is uric acid secretion, whereas GLU9 and URAT1 also ensure reabsorption. Pathogenic allelic variants in SLC2A9 and SLC22A12 are not only associated with hyperuricemia and gout, but they also lead to rare hereditary renal hypouricemia (type 1 – OMIM #220150 or type 2 – OMIM # 612076).
Objectives Previously, we analyzed ABCG2 gene and detected non-synonymous variants that lead to hyperuricemia and early onset of the gout.1 The aim of this study was to find a possible correlation between variants in SLC2A9 and SLC22A12 and hypouricemia, hyperuricemia and gout.2
Methods We recruited a cohort of 232 individuals with primary gout and hyperuricemia. We examined coding regions of SLC2A9 (13 exons) and SLC22A12 (10 exons) by Sanger sequencing. We also analyzed SLC2A9 and SLC22A12 in five patients with suspect hypouricemia.
Results In the cohort of 232 individuals, we detected five synonymous variants, 18 intron variants and seven missense variants in SLC2A9: A17T, G25R, T275M, D281H, V282I, R294H, and P350L. In SLC22A12 gene, we found six synonymous variants and seven intron variants.
We detected several pathogenic variants in patients with suspect hypouricemia. Intronic variant c.1419+1G>A in SLC2A9 most likely affects the splicing. In SLC22A12, we found rare pathogenic variants T467M and L415_G417del. These variants have according to our previous study high frequency in the Czech and Slovak Roma population.3
Conclusions The uric acid level is determined by a complex mechanism that is not yet fully understood. Disorders of urate transporters can not only lead to hyperuricemia, but in rare cases also to hypouricemia.
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Acknowledgements This study was supported by the grant from the Czech Republic Ministry of Health AZV 15-26693A.
Disclosure of Interest None declared.
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