Patients with deficient hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity present hyperuricemia and/or hyperuricosuria, with a variable degree of neurological manifestations.
The SLC2A9 mutation increases the risk for T2DM complicated HUA in Chinese population, which suggested that intron variants between two relatively conserved exons could also be associated with diseases.
Three SNPs, URAT1 rs11231825, GLUT9 rs16890979 and ABCG2rs2231142, 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.
Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and <i>In Vitro</i> Verification with Cells.
Moreover, we found the significant decrease in protein expression of URAT1 and GLUT9, and the significant increase in protein expression of OAT1 in the kidney in AFPR treated groups compared to the model groups of hyperuricemia.
Plasma membrane expression of breast cancer resistance protein (BCRP), a uric acid efflux transporter, was decreased under hyperuricemia, though the total cellular expression of BCRP remained constant.
Predictors of ULT misuse included the percentage of patients having gout (1-10%: OR=5.40, p=0.047) or receiving ULT (greater than 10-20%: OR=20.02, p=0.001)among patients seen in clinic, attendance of rheumatology conferences (OR=2.55, p=0.017), and having a close relative with hyperuricemia or gout (OR=2.45, p=0.026).
Systematic analysis of Glut9 mutants confirms Glut9 as putative target for the treatment of hyperuricemia and brings new insights in Glut9 structure - function.
Adenosine 5'-triphosphate-binding cassette subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K (rs2231142), are risk factors for hyperuricemia and gout.
Common dysfunctional variants of ATP binding cassette subfamily G member 2 (Junior blood group) (ABCG2), a high-capacity urate transporter gene, that result in decreased urate excretion are major causes of hyperuricemia and gout.
G. pensylvanicum extract showed activity in reducing serum uric acid (Sur) through effect renal glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1) and urate transporter 1 (URAT1) mainly and inhibited XO activity in vivo of mice with PO induced hyperuricemia.
Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations.
However, compared to the hyperuricemia control, OAT1 was elevated remarkably in mice drugged with GAE and GAW, while GLUT9 was significantly decreased.
Not only does the 141K polymorphism in ABCG2 lead to hyperuricemia through renal overload and renal underexcretion, but emerging evidence indicates that it also increases the risk of acute gout in the presence of hyperuricemia, early onset of gout, tophi formation, and a poor response to allopurinol.
Previous genome-wide association studies have found that the ABCG2 single nucleotide polymorphism (SNP) rs2231142 is an important genetic factor for increased uric acid (UA) levels, and the degree of association between rs2231142 and hyperuricemia is affected by both sex and ethnicity.
ABCG2 and a novel gene, SLC17A4, contributed to the development of gout from hyperuricemia (OR = 1.56, P<sub>FDR</sub> = 3.68E-09; OR = 1.27, P<sub>FDR</sub> = 0.013, respectively).