XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
67.
ANALYSIS OF UraTE TraNSPORTERS SLC22A12 aND SLC2A9 IN PATIENTS
WITH RENAL HYPOURICEMIA IN CZECH POPULATION
Blanka Stibůrková 1 , Makoto Hosoyamada 3 , Kimiyoshi Ichida 4 and Ivan Šebesta 1,2
1
Charles University in Prague, First Faculty of Medicine, Institute of Inherited Metabolic
Disorders and 2 Institute of Clinical Biochemistry and Laboratory Medicine; 3 Division of
Pharmacotherapeutics, Faculty of Pharmacy, Keio University, Tokyo; 4 Department of
Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Japan
Renal hypouricemia is a heterogeneous inherited disorder characterised by impaired
tubular uric acid transport, reabsorption insufficiency and/or acceleration of secretion
(OMIM #220150) with severe complications such as acute renal failure and nephrolithiasis.
The most causative genes are SLC22A12 and SLC2A9. We have selected 14 patients from
10 families for analysis of the SLC22A12 and SLC2A9 from the group of 569 hypouricemic
cases. Sequence analysis of SLC22A12 revealed three transitions G366R, T467M, R477H and
one deletion A416_L418del in seven heterozygotes, three compound hetero-zygotes and
four homozygotes. Sequence analysis of SLC2A9 revealed three unpublished transitions
G216R, D281H, N333S, one insertion with frame shifting change p.[I118HfsX27] and four
published sequence variants G25R, V282I, R294H and P350L in two heterozygotes, five
compound heterozygotes and two homozygotes. The function and immunohistochemistry
analysis in Xenopus laevis oocytes including subcellular localization, colocalization and
processing dynamics and transport of proteins are in process.
Our finding supports the prediction that intact function of both SLC22A12 and SLC2A9
transporters is necessary for normal urate reabsorption. Further detailed studies could
clarify genotype/phenotype relations in hypo/hyper-uricemia and gout and in conditions
related to hyperuricemia as well.
Acknowledgement: Acknowledgement: Supported by grants MSM0021620806 and IGA
MZ 11322 – 4 /2010, Czech Republic.
XXII. Biochemistry Congress, Martin
189