GLUT9 influences uric acid concentration in patients with Lesch-Nyhan disease.

Publisher: Wiley on behalf of the Asia Pacific League of Associations for Rheumatology Country of Publication: England NLM ID: 101474930 Publication Model: Print Cited Medium: Internet ISSN: 1756-185X (Electronic) Linking ISSN: 17561841 NLM ISO Abbreviation: Int J Rheum Dis Subsets: MEDLINE

Original Publication: [Oxford, UK] : Wiley on behalf of the Asia Pacific League of Associations for Rheumatology

Polymorphism, Single Nucleotide*; Glucose Transport Proteins, Facilitative/*genetics ; Gout/*genetics ; Hyperuricemia/*genetics ; Lesch-Nyhan Syndrome/*genetics ; Uric Acid/*blood; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics ; Adolescent ; Adult ; Allopurinol/therapeutic use ; Biomarkers/blood ; Child ; Child, Preschool ; Genetic Predisposition to Disease ; Glucose Transport Proteins, Facilitative/metabolism ; Gout/blood ; Gout/diagnosis ; Gout/drug therapy ; Gout Suppressants/therapeutic use ; Humans ; Hyperuricemia/blood ; Hyperuricemia/diagnosis ; Hyperuricemia/drug therapy ; Lesch-Nyhan Syndrome/blood ; Lesch-Nyhan Syndrome/diagnosis ; Lesch-Nyhan Syndrome/drug therapy ; Middle Aged ; Neoplasm Proteins/genetics ; Organic Anion Transporters/genetics ; Organic Cation Transport Proteins/genetics ; Phenotype ; Renal Elimination ; Treatment Outcome ; Young Adult

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 (SNPs), including those of the GLUT9, ABCG2 and URAT1 genes, have been described that influence the renal handling of uric acid and modulate serum urate levels. In the present study, we analyzed whether GLUT9, ABCG2 and URAT1 gene SNPs are able to influence uric acid levels and allopurinol response in patients with HPRT deficiency.
Methods: Three SNPs, URAT1 rs11231825, GLUT9 rs16890979 and ABCG2 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 GLUT9 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 ABCG2 gene or rs11231825 in the URAT1 gene and serum urate levels or allopurinol response was found in our patients with HPRT deficiency.
Conclusions: GLUT9 SNPs 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.
(© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Keywords: BCRP; HPRT; ABCG2; GLUT9; Lesch-Nyhan; SLC22A12; SLC2A9; URAT1; allopurinol; hyperuricemia

0 (ABCG2 protein, human)
0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
0 (Biomarkers)
0 (Glucose Transport Proteins, Facilitative)
0 (Gout Suppressants)
0 (Neoplasm Proteins)
0 (Organic Anion Transporters)
0 (Organic Cation Transport Proteins)
0 (SLC22A12 protein, human)
0 (SLC2A9 protein, human)
268B43MJ25 (Uric Acid)
63CZ7GJN5I (Allopurinol)

Date Created: 20180608 Date Completed: 20181015 Latest Revision: 20181202

20250114

10.1111/1756-185X.13323

29879316