Rosa J. Torres, A. Sanchez, A. Menendez
Affiliation(s):
Departments of Biochemistry and Internal Medicine, La Paz University Hospital, IdiPaz, Madrid, Spain Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain
Objective: Patients with complete or partial deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity presented hyperuricemia and/or hyperuricosuria, and a variable degree of neurological manifestations. Hyperuricemia in HPRT deficiency is due to uric acid overproduction and is treated with the xanthine oxidase inhibitor allopurinol. Renal uric acid excretion is striking increased in these patients, and allopurinol doses should be adjusted to avoid xanthine lithiasis. In recent years, several renal tubular urate transporter single nucleotide polymorphisms (SNPs), including those of the SLC2A9, ABCG2, and SLC22A12 genes, have been described that influences the renal handling of uric acid and modulates serum urate levels. In the present study, we have analyzed if SLC2A9, ABCG2, and SLC22A12 genes SNPs are able to influence uric acid levels and allopurinol response in patients with HPRT deficiency.
Methods: Three SNPs, SLC22A12 rs11231825, SLC2A9 rs16890979, and ABCG2 rs2231142, previously associated in our population with hyperuricemia and gout, were analyzed in 27 patients with HPRT deficiency treated with allopurinol during at least 5 years.
Results: HPRT deficient patients with allele A of rs16890979 of SLC2A9 gene presented a lower serum urate concentration at diagnosis, before allopurinol treatment was instituted, and needed a lower allopurinol doses to maintain serum urate levels between 268 and 446 µmol/l (4.5 and 7.5 mg/dL). No relationship between the rs2231142 in ABCG2 gene, and the rs11231825 in SLC22A12 gene, and serum urate levels or allopurinol response was found in our HPRT deficient patients.
Conclusions: SLC2A9 influences the renal handling of uric acid, and modulates serum urate levels and response to alopurinol treatment, in patients with uric acid overproduction due to HPRT deficiency.