URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia

Long-term effects of the SLC2A9 G844A and SLC22A12 C246T variants on serum uric acid concentrations in children

“…A meta-analysis of GWA studies identified multiple candidate loci related to UA level in European ( SLC2A9 , ABCG2 , SLC17A1 , SLC22A11 , SLC22A12 , SLC16A9 , GCKR , LRRC16A , and PDZK1 ) and East Asian ( SLC2A9 , ABCG2 , SLC22A12 , and MAF ) populations [ 2 , 25 ]. Mutations in SLC22A12 or SLC2A9 were initially reported in Japanese patients with renal hypouricemia, although patients from various ethnic groups have subsequently been identified [ 7 ]. A study of children in the Viva La Familia Study also recently showed that the serum UA concentration was associated strongly with genetic variants in SLC2A9 through GWA analysis [ 19 ].…”

“…Genome-wide association (GWA) studies of common variants identified more than 30 genetic loci associated with the UA concentrations, mostly in urate transporters, such as the genes encoding solute carrier family 2 facilitated glucose transporter member 9 (also known as SLC2A9 encoding GLUT9), solute carrier family 22 (organic anion/cation transporter) member 12 (also known as SLC22A12 encoding URAT1), and the ATP-binding cassette transporter subfamily G member 2 ( ABCG2 ) [ 2 , 5 ]. The importance of URAT1 and GLUT9 for regulating blood urate levels was confirmed, and mutations in SLC22A12 and SLC2A9 have been reported to be responsible for hypouricemia [ 7 ]. ABCG2 is also known to be a major cause of gout and hyperuricemia that acts by decreasing urate excretion [ 8 ].…”

Amplicon targeted resequencing for SLC2A9 and SLC22A12 identified novel mutations in hypouricemia subjects

“…To summarize, SLC2A9: p.R90H allele accounted for 27.8% (5/9*2) among the hypouricemia patients which was much greater than that in Japan and Korea (Zhou et al, ), while W258X was not detected in any hypouricemia patient in Chinese samples. The SLC22A12 mutants were of major subtype responsibility for hRHUC, which was identical in varied ethnicities (Claverie‐Martin et al, ; Zhou et al, ). The high incidence of hRHUC1 (OMIM #220150) has been reported in the Asian region and is attributed to the high frequency of the p.W258X (2.30%–2.37%) and p.R90H (0.40%) in SLC22A12 among Japanese (Iwai et al, ; Taniguchi et al, ) and general Korean populations (Lee et al, ), which is indicative of a founder mutation in the Asian continent.…”

“…Reference ranges of SUA: children under 15 years of age and adult females, 2.0-5.7 mg/dl (120-342 µmol/L); adult males, 2.0-7.0 mg/dl (120-420 µmol/L) (Stiburkova et al, 2013). Hypouricemia was defined as SUA ≤2 mg/dl (120 µmol/L) irrespective of sex (Claverie-Martin et al, 2018;Gibson, Sims, & Jimenez, 1976;Ichida et al, 2004). HUA was defined as | 3 of 14 ZHOU et al…”

“…Among them, hereditary renal hypouricemia (hRHUC) is a major type due to mutations of urate transporter URAT1 (encoded by SLC22A12 [OMIM *607096] and classified as hRHUC 1 [OMIM #220150]) and URATv1 (encoded by SLC2A9 [OMIM *606142] and classified as hRHUC 2 [OMIM #612076]) and is prone to exercise-induced acute renal failure (EIARF) and urolithiasis especially in men (Ichida et al, 2008;Kaito et al, 2013). Recently, hRHUC patients complicated with chronic renal failure have been reported (Aksoy, Koyun, Ichida, Comak, & Akman, 2018a, 2018bClaverie-Martin et al, 2018) and the correlation of hypouricemia with reduced kidney function was also established in a large-scale cross-sectional populationbased study (Wakasugi et al, 2015). Therefore, recognizing people with very low SUA and providing prompt medical guidance is of critical importance to avoid renal adverse events (Bhasin et al, 2014).…”