Dataset Information

Association of Serum Uric Acid with Metabolic Syndrome and Its Components: A Mendelian Randomization Analysis.

ABSTRACT: The role of uric acid on metabolic syndrome (MetS) has always been controversial. This study aims to explore associations between uric acid with MetS and its components in Chinese female health check-up population. 1381 subjects constituted the longitudinal health check-up cohort. Health examination and genotyping were performed. Unadjusted and adjusted observational analyses were implemented to evaluate observational associations between uric acid with MetS and its components. Mendelian randomization analysis was performed to estimate the causal effect using variation at rs11722228 (SLC2A9) as an instrument for uric acid. An increase of 65% in risk of MetS per standard deviation increase in uric acid was found using unadjusted observational analyses. This association attenuated on adjustment for potential confounders. Similar patterns were found in the association analyses of uric acid with hyperglycemia, hypertension, and dyslipidemia. Neither by performing unadjusted nor adjusted analysis did we see evidence for association of uric acid on overweight and obesity. Mendelian randomization analyses showed no evidence of causal association between uric acid and MetS and MetS components. We found no causal evidence to support that increased serum uric acid is a causal risk factor for MetS or its components. Hence, there remains no strong evidence for the effeteness of undergoing urate-lowering therapy to prevent the onset of MetS or cardiovascular disease in health management.

SUBMITTER: Wang L

PROVIDER: S-EPMC7063870 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of Serum Uric Acid with Metabolic Syndrome and Its Components: A Mendelian Randomization Analysis.

Wang Lu L Zhang Tao T Liu Yafei Y Tang Fang F Xue Fuzhong F

BioMed research international 20200222

<h4>Background</h4>The role of uric acid on metabolic syndrome (MetS) has always been controversial. This study aims to explore associations between uric acid with MetS and its components in Chinese female health check-up population.<h4>Methods</h4>1381 subjects constituted the longitudinal health check-up cohort. Health examination and genotyping were performed. Unadjusted and adjusted observational analyses were implemented to evaluate observational associations between uric acid with MetS and ...[more]

PMID: 32258131

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Project description:ObjectiveHyperuricaemia and gout are common metabolic disorders. However, the causal relationships between blood metabolites and serum urate levels, as well as gout, remain unclear. A systematic evaluation of the causal connections between blood metabolites, hyperuricemia, and gout could enhance early screening and prevention of hyperuricemia and gout in clinical settings, providing novel insights and approaches for clinical treatment.MethodsIn this study, we employed a bidirectional two-sample Mendelian randomization analysis utilizing data from a genome-wide association study involving 7,286 participants, encompassing 486 blood metabolites. Serum urate and gout data were sourced from the Chronic Kidney Disease Genetics consortium, including 288,649 participants for serum urate and 9,819 African American and 753,994 European individuals for gout. Initially, LDSC methodology was applied to identify blood metabolites with a genetic relationship to serum urate and gout. Subsequently, inverse-variance weighting was employed as the primary analysis method, with a series of sensitivity and pleiotropy analyses conducted to assess the robustness of the results.ResultsFollowing LDSC, 133 blood metabolites exhibited a potential genetic relationship with serum urate and gout. In the primary Mendelian randomization analysis using inverse-variance weighting, 19 blood metabolites were recognized as potentially influencing serum urate levels and gout. Subsequently, the IVW p-values of potential metabolites were corrected using the false discovery rate method. We find leucine (IVW P FDR = 0.00004), N-acetylornithine (IVW P FDR = 0.0295), N1-methyl-3-pyridone-4-carboxamide (IVW P FDR = 0.0295), and succinyl carnitine (IVW P FDR = 0.00004) were identified as significant risk factors for elevated serum urate levels. Additionally, 1-oleoylglycerol (IVW P FDR = 0.0007) may lead to a substantial increase in the risk of gout. Succinyl carnitine exhibited acceptable weak heterogeneity, and the results for other blood metabolites remained robust after sensitivity, heterogeneity, and pleiotropy testing. We conducted an enrichment analysis on potential blood metabolites, followed by a metabolic pathway analysis revealing four pathways associated with serum urate levels.ConclusionThe identified causal relationships between these metabolites and serum urate and gout offer a novel perspective, providing new mechanistic insights into serum urate levels and gout.

Dataset Information

Association of Serum Uric Acid with Metabolic Syndrome and Its Components: A Mendelian Randomization Analysis.

Publications

Association of Serum Uric Acid with Metabolic Syndrome and Its Components: A Mendelian Randomization Analysis.

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