#2640 Hyperuricemia in Gitelman syndrome 132 patients

Abstract

Abstract Background and Aims Thiazide diuretics, the most common prescription for hypertension, were partly restricted by the hyperuricemia induced by the impairment of uric acid clearance serum uric acid. Gitelman syndrome (GS, OMIM263800), caused by mutations of the SLC12A3 gene encodes the thiazide-sensitive human Na–Cl co-transporter (hNCC), might shed light on the precision mechanism of hyperuricemia induced by Thiazide diuretics. Method We retrospectively reviewed 132 GS patients and pertinent articles and analyzed their clinical and genetic characteristics with or without hyperuricemia. Our study also employed Illumina Human Asian Screening Array-24 + v1.0 (ASA) gene chips to screen available samples from 87 patients with Gitelman Syndrome, which included a subgroup of 17 individuals exhibiting elevated uric acid levels characteristic of GS. Results The average uric acid level of 132 genetic-confirmed GS patients was 351.4 ± 95.1 µmol/l, with 21.2% hyperuricemia (mean 482.1 µmol/l) and 2 cases of gout. The GS patients with hyperuricemia had higher BMI (24.3 ± 3.9 vs. 21.6 ± 3.5 kg/m2, P = 0.001), lower FEUA (4.6 ± 1.0 vs. 7.0 ± 2.7%, P < 0.001), urinary calcium/creatinine (0.05 vs. 0.11 mmol/mmol, P = 0.01), and△FECl (0.6 ± 0.4% vs 1.2 ± 1.1%, P = 0.02) of the HCT test, indicating more severe NCC function injury. Fisher's exact test yielded non-significant associations of the ten uric acid-predicting SNPs between the patients with or without hyperuricemia at the conventional P-value cut-off of 0.05. Conclusion The prevalence of hyperuricemia in GS patients exceeds that observed in the general population. GS patients with hyperuricemia might be because of a high body mass index (BMI) and more severe impairment of NCC function, which suggested the crosstalk between NCC and Uric acid transporter.