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URAT1 inhibition by ALPK1 is associated with uric acid homeostasis.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2017 Apr 01; Vol. 56 (4), pp. 654-659. - Publication Year :
- 2017
-
Abstract
- Objective: The aim of this study was to identify a protein for urate transporter 1 (URAT1) regulation.<br />Methods: The clinical dataset consisted of 492 case-control samples of Han Chinese (104 gout and 388 controls). Three alpha kinase 1 ( ALPK1 ) and SLC22A12 loci associated with high gout risk and uric acid levels were genotyped. The overexpression of ALPK1 on URAT1 protein expression was evaluated in vivo in h ALPK1 transgenic mice. The in vitro protein levels of ALPK1 and URAT1 in ALPK1 small interfering RNA-transfected human kidney-2 cells with MSU crystal stimulation were examined.<br />Results: ALPK1 , which is a single nucleotide polymorphism (SNP) of rs11726117 (M861T; T), reduced the risk of gout via the SLC22A12 gene SNPs rs3825016 and rs475688, as compared with the subject of ALPK1 rs11726117 (C) allele {rs11726117 [CT + TT] vs rs3825016, odds ratio [OR] 0.39 [95% confidence interval (CI) 0.23, 0.67]; rs11726117 [CT + TT] vs rs475688, OR 0.39 [95% CI 0.23, 0.67]}. ALPK1-overexpressed mice demonstrated lower levels of URAT1 protein ( P = 0.0045). Mouse endogenous ALPK1 proteins were detected in renal proximal tubule cells. MSU crystals inhibited URAT1 expressions through an upregulation of ALPK1 in human kidney-2 cells.<br />Conclusion: Elevated ALPK1 expression decreased URAT1 expression. ALPK1 might prevent the impact of urate reuptake via SLC22A12 and appeared to be negatively associated with gout. ALPK1 is a potential repressor of URAT1 protein expression.<br /> (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)
- Subjects :
- Animals
Case-Control Studies
Cells, Cultured
Crystallization
Gout genetics
Homeostasis genetics
Homeostasis physiology
Humans
Hyperuricemia genetics
Hyperuricemia metabolism
Kidney Tubules, Proximal metabolism
Male
Mice, Inbred C57BL
Mice, Transgenic
Organic Anion Transporters genetics
Organic Anion Transporters metabolism
Organic Cation Transport Proteins genetics
Organic Cation Transport Proteins metabolism
Polymorphism, Single Nucleotide genetics
Protein Kinases genetics
Up-Regulation physiology
Gout metabolism
Organic Anion Transporters antagonists & inhibitors
Organic Cation Transport Proteins antagonists & inhibitors
Protein Kinases pharmacology
Uric Acid metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 56
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 28039413
- Full Text :
- https://doi.org/10.1093/rheumatology/kew463