GLUT9 inﬂuences uric acid concentration in patients with
Rosa J. TORRES
and Juan G. PUIG
La Paz University Hospital Health Research Institute (FIBHULP), IdiPaz, Madrid, Spain,
Center for Biomedical Network Research
on Rare Diseases (CIBERER), ISCIII, Spain, and
Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University
Hospital, IdiPaz, Madrid, Spain
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 allopuri-
nol 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 lmol/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.
Key words: ABCG2, allopurinol, BCRP, GLUT9, HPRT, hyperuricemia, Lesch–Nyhan, SLC22A12, SLC2A9,
(HPRT, EC 18.104.22.168) deﬁciency is a genetic disorder of
purine metabolism resulting from various mutations
in the X-chromosome-linked HPRT1 gene, encoding
the enzyme HPRT.
All patients with HPRT deﬁ-
ciency present with hyperuricemia and/or hyperurico-
Complete deﬁciency of HPRT activity results
in Lesch–Nyhan disease (LND, OMIM 300322), and
patients present with severe generalized dystonia,
choreoathetosis, cognitive deﬁcit and self-mutilation
Patients with Lesch–Nyhan variant (LNV,
OMIM 300323) present with partial deﬁciency of
HPRT activity, associated with variable degrees of
neurological manifestations, but without self-injurious
Correspondence: Dr Rosa J. Torres, MD, PhD, Ediﬁcio de Labo-
ratorios, Planta 3, Hospital Universitario ‘La Paz’, Paseo de la
Castellana 261. 28046 Madrid, Spain.
© 2018 Asia Paciﬁc League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd
International Journal of Rheumatic Diseases 2018; 21: 1270–1276