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GLUT 9 influences uric acid concentration in patients with Lesch‐Nyhan disease
Author(s) -
Torres Rosa J.,
Puig Juan G.
Publication year - 2018
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13323
Subject(s) - hyperuricemia , allopurinol , hypoxanthine guanine phosphoribosyltransferase , uric acid , gout , hypoxanthine , medicine , lesch–nyhan syndrome , endocrinology , hypoxanthine phosphoribosyltransferase , single nucleotide polymorphism , genotype , biology , biochemistry , gene , mutant , enzyme
Background Patients with deficient hypoxanthine‐guanine phosphoribosyltransferase ( HPRT ) activity present hyperuricemia and/or hyperuricosuria, with a variable degree of neurological manifestations. Hyperuricemia in HPRT deficiency is due to uric acid overproduction and is frequently treated with allopurinol. Renal uric acid excretion is sharply increased in these patients. In recent years, several renal tubular urate transporter single nucleotide polymorphisms ( SNP s), including those of the GLUT 9 , ABCG 2 and URAT 1 genes, have been described that influence the renal handling of uric acid and modulate serum urate levels. In the present study, we analyzed whether GLUT 9 , ABCG 2 and URAT 1 gene SNP s are able to influence uric acid levels and allopurinol response in patients with HPRT deficiency. Methods Three SNP s, URAT 1 rs11231825 , GLUT 9 rs16890979 and ABCG 2 rs2231142 , previously associated in our population with hyperuricemia and gout, were analyzed in 27 patients with HPRT deficiency treated with allopurinol for at least 5 years. Results Patients with HPRT deficiency having allele A of rs16890979 in the GLUT 9 gene present with a lower serum urate concentration at diagnosis, before allopurinol treatment is instituted, and need lower allopurinol doses to maintain serum urate levels between 268 and 446 μmol/L (4.5 and 7.5 mg/ dL ). No relationship between rs2231142 in the ABCG 2 gene or rs11231825 in the URAT 1 gene and serum urate levels or allopurinol response was found in our patients with HPRT deficiency. Conclusions GLUT 9 SNP s influence the renal handling of uric acid and modulate serum urate levels and the response to treatment in patients with uric acid overproduction due to HPRT deficiency.