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URAT1 inhibition by ALPK1 is associated with uric acid homeostasis.
Rheumatology (Oxford). 2017 04 01; 56(4):654-659.R

Abstract

Objective

The aim of this study was to identify a protein for urate transporter 1 (URAT1) regulation.

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.

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.

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Kuo TM
Environment-Omics-Disease Research Centre, China Medical University Hospital.
Huang CM
Graduate Institute of Integrated Medicine, China Medical University, Taichung.
Tu HP
Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Min-Shan Ko A
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
Wang SJ
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.
Lee CP
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.
Ko YC
Environment-Omics-Disease Research Centre, China Medical University Hospital. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.

MeSH

AnimalsCase-Control StudiesCells, CulturedCrystallizationGoutHomeostasisHumansHyperuricemiaKidney Tubules, ProximalMaleMice, Inbred C57BLMice, TransgenicOrganic Anion TransportersOrganic Cation Transport ProteinsPolymorphism, Single NucleotideProtein KinasesUp-RegulationUric Acid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28039413

Citation

Kuo, Tzer-Min, et al. "URAT1 Inhibition By ALPK1 Is Associated With Uric Acid Homeostasis." Rheumatology (Oxford, England), vol. 56, no. 4, 2017, pp. 654-659.
Kuo TM, Huang CM, Tu HP, et al. URAT1 inhibition by ALPK1 is associated with uric acid homeostasis. Rheumatology (Oxford). 2017;56(4):654-659.
Kuo, T. M., Huang, C. M., Tu, H. P., Min-Shan Ko, A., Wang, S. J., Lee, C. P., & Ko, Y. C. (2017). URAT1 inhibition by ALPK1 is associated with uric acid homeostasis. Rheumatology (Oxford, England), 56(4), 654-659. https://doi.org/10.1093/rheumatology/kew463
Kuo TM, et al. URAT1 Inhibition By ALPK1 Is Associated With Uric Acid Homeostasis. Rheumatology (Oxford). 2017 04 1;56(4):654-659. PubMed PMID: 28039413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - URAT1 inhibition by ALPK1 is associated with uric acid homeostasis. AU - Kuo,Tzer-Min, AU - Huang,Chung-Ming, AU - Tu,Hung-Pin, AU - Min-Shan Ko,Albert, AU - Wang,Shu-Jung, AU - Lee,Chi-Pin, AU - Ko,Ying-Chin, PY - 2016/04/15/received PY - 2017/1/1/pubmed PY - 2017/6/27/medline PY - 2017/1/1/entrez KW - ALPK1 KW - MSU KW - URAT1 KW - gout KW - hyperuricaemia SP - 654 EP - 659 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 56 IS - 4 N2 - Objective: The aim of this study was to identify a protein for urate transporter 1 (URAT1) regulation. 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. 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. 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. SN - 1462-0332 UR - https://www.unboundmedicine.com/medline/citation/28039413/URAT1_inhibition_by_ALPK1_is_associated_with_uric_acid_homeostasis_ DB - PRIME DP - Unbound Medicine ER -