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Article ; Online: Prevalence and Associations Between Metabolic Syndrome Components and Hyperuricemia by Race: Findings From US Population, 2011-2020.

Kim, Yun Jin / Kim, Sunghwan / Seo, Ji Hwan / Cho, Sung Kweon

2024

Abstract: Objective: We explored the trend in prevalence of hyperuricemia and metabolic syndrome in US populations and investigated associations between components of metabolic syndrome and hyperuricemia by race.: Methods: We analyzed data from the four most ... ...

Abstract	Objective: We explored the trend in prevalence of hyperuricemia and metabolic syndrome in US populations and investigated associations between components of metabolic syndrome and hyperuricemia by race. Methods: We analyzed data from the four most recent National Health and Nutrition Examination Survey (NHANES) cycles (2011 to March 2020), comprising 10,175 participants. Hyperuricemia is defined as serum urate >7.0 mg/dL (men) or >5.7 mg/dL (women), following the NHANES-III guideline. The definition of metabolic syndrome follows the National Cholesterol Education Program's Adult Treatment Panel III guideline. We estimated the prevalence of metabolic syndrome and hyperuricemia in each cycle and performed subgroup analyses with logistic regression to investigate the patterns of associated components of metabolic syndrome with hyperuricemia. Results: In the most recent cycle (2017 to March 2020), the prevalence of metabolic syndrome was 45.9% and that of hyperuricemia was 20.7%. Over the 2011 to 2020 period, a significant rise in metabolic syndrome prevalence was observed among Hispanic and Asian populations, and the prevalence of hyperuricemia has increased significantly only in the Hispanic population. After adjustment for confounding factors, patients with metabolic syndrome exhibited a higher hyperuricemia in women than in men. Elevated blood pressure was the strongest factor with hyperuricemia. The association was the weakest in the Asian population. Waist circumference was the only significant factor associated with hyperuricemia in the Asian population. Conclusion: The prevalence of metabolic syndrome has an increasing pattern, but there was no specific decadal trend in prevalence of hyperuricemia. There is an ethnicity-specific association of metabolic syndrome and hyperuricemia, especially among Asians.
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	645059-3
ISSN	2151-4658 ; 0893-7524 ; 2151-464X
ISSN (online)	2151-4658
ISSN	0893-7524 ; 2151-464X
DOI	10.1002/acr.25338
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Article ; Online: The in-silico evaluation of important GLUT9 residue for uric acid transport based on renal hypouricemia type 2.

Cachau, Raul / Shahsavari, Shahin / Cho, Sung Kweon

Chemico-biological interactions

2023 Volume 373, Page(s) 110378

Abstract: Uric acid is the end product of purine metabolism. Uric acid transporters in the renal proximal tubule plays a key role in uric acid transport. Functional abnormalities in these transporters could lead to high or low levels of uric acid in the blood ... ...

Abstract	Uric acid is the end product of purine metabolism. Uric acid transporters in the renal proximal tubule plays a key role in uric acid transport. Functional abnormalities in these transporters could lead to high or low levels of uric acid in the blood plasma, known as hyperuricemia and hypouricemia, respectively. GLUT9 has been reported as a key transporter for uric acid reuptake in renal proximal tubule. GLUT9 mutation is known as causal gene for renal hypouricemia due to defective uric acid uptake, with more severe cases resulting in urolithiasis and exercise induced acute kidney injury (EIAKI). However, the effect of mutation is not fully investigated and hard to predict the change of binding affinity. We comprehensively described the effect of GLUT9 mutation for uric acid transport using molecular dynamics and investigated the specific site for uric acid binding differences. R171C and R380W showed the significant disruption of the structure not affecting transport dynamics whereas L75R, G216R, N333S, and P412R showed the reduced affinity of the extracellular vestibular area towards urate. Interestingly, T125 M showed a significant increase in intracellular binding energy, associated with distorted geometries. We can use this classification to consider the effect mutations by comparing the transport profiles of mutants against those of chemical candidates for transport and providing new perspectives to urate lowering drug discovery using GLUT9.
MeSH term(s)	Humans ; Uric Acid/metabolism ; Glucose Transport Proteins, Facilitative/chemistry ; Glucose Transport Proteins, Facilitative/genetics ; Glucose Transport Proteins, Facilitative/metabolism ; Urinary Calculi/genetics ; Mutation ; Membrane Transport Proteins/genetics ; Organic Anion Transporters/genetics
Chemical Substances	Uric Acid (268B43MJ25) ; Glucose Transport Proteins, Facilitative ; Membrane Transport Proteins ; Organic Anion Transporters
Language	English
Publishing date	2023-02-01
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	218799-1
ISSN	1872-7786 ; 0009-2797
ISSN (online)	1872-7786
ISSN	0009-2797
DOI	10.1016/j.cbi.2023.110378
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Article ; Online: Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval.

Choi, Hee Sun / Choi, A Young / Kopp, Jeffrey B / Winkler, Cheryl A / Cho, Sung Kweon

Journal of Korean medical science

2024 Volume 39, Issue 14, Page(s) e134

Abstract: The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of ... ...

Abstract	The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. In all, 387 drugs were found for initial review. After removing unrelated trials and drugs, 66 drugs were selected, including 17 approved drugs and 49 drugs under development. These drugs were classified into six categories: 1) drugs targeting the viral life cycle 2) Anti-severe acute respiratory syndrome coronavirus 2 Monoclonal Antibodies, 3) immunomodulators, 4) anti-coagulants, 5) COVID-19-induced neuropathy drugs, and 6) other therapeutics. Among the 49 drugs under development are the following: 6 drugs targeting the viral life cycle, 12 immunosuppression drugs, 2 immunostimulants, 2 HIF-PHD targeting drugs, 3 GM-CSF targeting drugs, 5 anti-coagulants, 2 COVID-19-induced neuropathy drugs, and 17 others. This review provides insight into mechanisms of action, properties, and indications for COVID-19 medications.
MeSH term(s)	United States ; Humans ; COVID-19 ; SARS-CoV-2 ; COVID-19 Vaccines/therapeutic use ; Antiviral Agents/therapeutic use ; Antiviral Agents/pharmacology ; Antibodies, Viral ; Pharmaceutical Preparations
Chemical Substances	COVID-19 Vaccines ; Antiviral Agents ; Antibodies, Viral ; Pharmaceutical Preparations
Language	English
Publishing date	2024-04-15
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	639262-3
ISSN	1598-6357 ; 1011-8934
ISSN (online)	1598-6357
ISSN	1011-8934
DOI	10.3346/jkms.2024.39.e134
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Article: Review of Urate-Lowering Therapeutics: From the Past to the Future.

Jenkins, Christopher / Hwang, Jennifer H / Kopp, Jeffrey B / Winkler, Cheryl A / Cho, Sung Kweon

Frontiers in pharmacology

2022 Volume 13, Page(s) 925219

Abstract: We reviewed all currently available ULT, as well as any medications in development using following databases: United States Food and Drug Administration (FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), ... ...

Abstract	We reviewed all currently available ULT, as well as any medications in development using following databases: United States Food and Drug Administration (FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. We identified a total of 36 drugs, including 10 approved drugs, 17 in clinical testing phases, and 9 in preclinical developmental phases. The 26 drugs currently undergoing testing and development include 5 xanthine oxidase inhibitors, 14 uricosurics, 6 recombinant uricases, and one with multiple urate-lowering mechanisms of action. Herein, we reviewed the benefit and risk of each drug summarizing currently available drugs. New trials of uricosuric agents are underway to develop the new indication. New drugs are going on to improve the potency of recombinant uricase and to develop the new route administration of such as oral formulation. This review will provide valuable information on the properties, indications, and limitations of ULTs.
Language	English
Publishing date	2022-08-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.925219
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Article: The MATE1 rs2289669 polymorphism affects the renal clearance of metformin following ranitidine treatment.

Cho, Sung Kweon / Chung, Jae-Yong

International journal of clinical pharmacology and therapeutics

2016 Volume 54, Issue 4, Page(s) 253–262

Abstract: Purpose: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin. The goal ... ...

Abstract	Purpose: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin. The goal of this study was to determine the association between metformin's pharmacokinetics and pharmacodynamics and the genetic variants of MATE1 (rs2289669) and OCT2 (rs316019) before and after treatment with the potential MATE inhibitor, ranitidine. Methods: We recruited 26 healthy Koreans balanced across the OCT2 and MATE1 genetic variants, and conducted a prospective clinical trial to investigate their effects on metformin's pharmacokinetics and pharmacodynamics before and after ranitidine treatment. Results: Neither MATE1 rs2289669 nor OCT2 rs316019 affected metformin's pharmacokinetics and pharmacodynamics before ranitidine treatment. However, the renal clearance of metformin was significantly higher (15.2%) after ranitidine treatment in the MATE1 GG group compared with the MATE1 GA + AA group. Only the effect of MATE1 on the renal clearance of metformin after ranitidine treatment was significant (b = -0.465, p ≤ 0.05) after including demographic data and the OCT2 genotype in the model. Conclusion: Our study suggests that MATE1 rs2289669 may be a significant determinant in the renal clearance of metformin in the case of transporter-mediated drug interactions.
MeSH term(s)	Adult ; Drug Interactions ; Female ; Humans ; Hypoglycemic Agents/pharmacokinetics ; Kidney/metabolism ; Male ; Metabolic Clearance Rate ; Metformin/pharmacokinetics ; Organic Cation Transport Proteins/antagonists & inhibitors ; Organic Cation Transport Proteins/genetics ; Organic Cation Transporter 2 ; Polymorphism, Genetic ; Prospective Studies ; Ranitidine/pharmacology
Chemical Substances	Hypoglycemic Agents ; Organic Cation Transport Proteins ; Organic Cation Transporter 2 ; SLC22A2 protein, human ; SLC47A1 protein, human ; SLC47A2 protein, human ; Ranitidine (884KT10YB7) ; Metformin (9100L32L2N)
Language	English
Publishing date	2016-01-14
Publishing country	Germany
Document type	News ; Research Support, Non-U.S. Gov't
ZDB-ID	124384-6
ISSN	0946-1965 ; 0340-0026 ; 0300-9718 ; 0174-4879
ISSN	0946-1965 ; 0340-0026 ; 0300-9718 ; 0174-4879
DOI	10.5414/CP202473
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Article: The 120-minute oral glucose tolerance test is sufficient for the evaluation of metformin's glucose-lowering effect in healthy volunteers.

Cho, Sunghwa / Son, Hyekyung / Cho, Sung Kweon

International journal of clinical pharmacology and therapeutics

2018 Volume 56, Issue 3, Page(s) 151–154

MeSH term(s)	Blood Glucose/drug effects ; Glucose Tolerance Test/methods ; Humans ; Hypoglycemic Agents/pharmacology ; Metformin/pharmacology ; Time Factors
Chemical Substances	Blood Glucose ; Hypoglycemic Agents ; Metformin (9100L32L2N)
Language	English
Publishing date	2018-03
Publishing country	Germany
Document type	Comparative Study ; Journal Article
ZDB-ID	124384-6
ISSN	0946-1965 ; 0340-0026 ; 0300-9718 ; 0174-4879
ISSN	0946-1965 ; 0340-0026 ; 0300-9718 ; 0174-4879
DOI	10.5414/CP203019
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Article: Efficacy of Xanthine Oxidase Inhibitors in Lowering Serum Uric Acid in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Lee, Yoojin / Hwang, Jennifer / Desai, Shaan H / Li, Xiaobai / Jenkins, Christopher / Kopp, Jeffrey B / Winkler, Cheryl A / Cho, Sung Kweon

Journal of clinical medicine

2022 Volume 11, Issue 9

Abstract: Objective: Current guidelines for gout recommend a treat-to-target approach with serum uric acid (SUA). However, there is little evidence for the dose-dependent effects of urate-lowering therapy (ULT). Herein, we analyzed the reported SUA-lowering effect ...

Abstract	Objective: Current guidelines for gout recommend a treat-to-target approach with serum uric acid (SUA). However, there is little evidence for the dose-dependent effects of urate-lowering therapy (ULT). Herein, we analyzed the reported SUA-lowering effect and SUA target achievement differences for various doses of xanthine oxidase inhibitors. Methods: Approved ULT drugs were selected from the FDA Drug Database. We included prospective randomized controlled trials of ULT drugs from ClinicalTrials.gov, articles published in the journal “Drugs”, and Embase, a literature database. A meta-analysis was performed to determine the ability of different ULT drugs and doses to lower and maintain a target SUA < 6 mg/dL. Results: We identified 35 trials including 8172 patients with a baseline SUA of 8.92 mg/dL. The allopurinol, febuxostat, and topiroxostat showed dose-proportional SUA-lowering responses. Compared with allopurinol 300 mg daily, febuxostat 80 mg daily and 120 mg daily more effectively maintained SUA < 6 mg/dL. Conclusion: Allopurinol, febuxostat, and topiroxostat showed dose-proportional ability to lower and achieve a target SUA < 6 mg/dL. Significance and Innovations. We showed dose-dependent SUA lowering effects of allopurinol, febuxostat, and topiroxostat. Febuxostat is effective at ULT compared to allopurinol and could be potentially offered as an alternative agent when patients (1) have CKD, (2) have the human leukocyte antigen HLA-B*5801 allele, and (3) become refractory to allopurinol. Gradual allopurinol dose increase with a lower starting dose is needed in CKD.
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11092468
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Article ; Online: Large-scale cross-ancestry genome-wide meta-analysis of serum urate.

Cho, Chamlee / Kim, Beomsu / Kim, Dan Say / Hwang, Mi Yeong / Shim, Injeong / Song, Minku / Lee, Yeong Chan / Jung, Sang-Hyuk / Cho, Sung Kweon / Park, Woong-Yang / Myung, Woojae / Kim, Bong-Jo / Do, Ron / Choi, Hyon K / Merriman, Tony R / Kim, Young Jin / Won, Hong-Hee

Nature communications

2024 Volume 15, Issue 1, Page(s) 3441

Abstract: Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate ... ...

Abstract	Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.
MeSH term(s)	Humans ; DNA-Binding Proteins/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Gout/genetics ; Gout/blood ; Heart Failure/genetics ; Heart Failure/blood ; Hypertension/genetics ; Hypertension/blood ; Hyperuricemia/genetics ; Hyperuricemia/blood ; Mendelian Randomization Analysis ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide ; Transcriptome ; Uric Acid/blood
Chemical Substances	DNA-Binding Proteins ; Uric Acid (268B43MJ25)
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47805-4
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Article: Identification of a dysfunctional exon-skipping splice variant in

Toyoda, Yu / Cho, Sung Kweon / Tasic, Velibor / Pavelcová, Kateřina / Bohatá, Jana / Suzuki, Hiroshi / David, Victor A / Yoon, Jaeho / Pallaiova, Anna / Šaligová, Jana / Nousome, Darryl / Cachau, Raul / Winkler, Cheryl A / Takada, Tappei / Stibůrková, Blanka

Frontiers in genetics

2023 Volume 13, Page(s) 1048330

Abstract: Renal hypouricemia (RHUC) is a pathological condition characterized by extremely low serum urate and overexcretion of urate in the kidney; this inheritable disorder is classified into type 1 and type 2 based on causative genes encoding physiologically- ... ...

Abstract	Renal hypouricemia (RHUC) is a pathological condition characterized by extremely low serum urate and overexcretion of urate in the kidney; this inheritable disorder is classified into type 1 and type 2 based on causative genes encoding physiologically-important urate transporters,
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2022.1048330
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Article ; Online: U-Shaped Association Between Serum Uric Acid Level and Risk of Mortality: A Cohort Study.

Cho, Sung Kweon / Chang, Yoosoo / Kim, Inah / Ryu, Seungho

Arthritis & rheumatology (Hoboken, N.J.)

2018 Volume 70, Issue 7, Page(s) 1122–1132

Abstract: Objective: In addition to the controversy regarding the association of hyperuricemia with cardiovascular disease (CVD) mortality, few studies have examined the impact of a low uric acid level on mortality. We undertook the present study to evaluate the ... ...

Abstract	Objective: In addition to the controversy regarding the association of hyperuricemia with cardiovascular disease (CVD) mortality, few studies have examined the impact of a low uric acid level on mortality. We undertook the present study to evaluate the relationship between both low and high uric acid levels and the risk of all-cause and cause-specific mortality in a large sample of Korean adults over a full range of uric acid levels. Methods: A cohort study was performed in 375,163 South Korean men and women who underwent health check-ups from 2002 to 2012. Vital status and cause of death were ascertained from the national death records. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality outcomes were estimated using Cox proportional hazards regression analysis. Results: During a total of 2,060,721.9 person-years of follow-up, 2,020 participants died, with 287 CVD deaths and 963 cancer deaths. Low and high uric acid levels were associated with increased all-cause, CVD, and cancer mortality. The multivariable-adjusted HRs for all-cause mortality in the lowest uric acid categories (<3.5 mg/dl for men and <2.5 mg/dl for women) compared with the sex-specific reference category were 1.58 (95% CI 1.18-2.10) and 1.80 (95% CI 1.10-2.93), respectively. Corresponding HRs in the highest uric acid categories (≥9.5 mg/dl for men and ≥8.5 mg/dl for women) were 2.39 (95% CI 1.57-3.66) and 3.77 (95% CI 1.17-12.17), respectively. Conclusion: In this large cohort study of men and women, both low and high uric acid levels were predictive of increased mortality, supporting a U-shaped association between serum uric acid levels and adverse health outcomes.
MeSH term(s)	Adult ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/mortality ; Cause of Death ; Female ; Humans ; Hyperuricemia/blood ; Hyperuricemia/mortality ; Male ; Middle Aged ; Proportional Hazards Models ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Uric Acid/blood
Chemical Substances	Uric Acid (268B43MJ25)
Language	English
Publishing date	2018-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.40472
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