Association between uric acid and aortic aneurysms: A two-sample Mendelian randomization study

High serum uric acid (UA) levels have been linked to cancer development through chronic inflammation and oxidative damage. Traditional epidemiological studies have shown inconsistent results regarding the relationship between uric acid and gynecological cancers. This study uses Mendelian randomization (MR) to explore the potential association between serum UA levels and various gynecological cancers. In this two-sample MR study, summary statistical data of the genome-wide association studies (GWASs) on serum UA levels were extracted from the UK Biobank (UKB), and those on gynecological cancers were obtained from the FinnGen consortium, the Epidemiology of Endometrial Cancer Consortium (E2C2), and the Ovarian Cancer Association Consortium (OCAC). Inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and MR-Radial methods were utilized to investigate the bidirectional causal associations of serum UA levels with gynecological cancers. The evaluation indexes were odds ratios (ORs) and confidence intervals (CIs). Tests for horizontal pleiotropism and heterogeneity of instrumental variables (IVs) were performed, respectively using MR-Egger test and Cochran's Q statistics. In addition, leave-one-out and MR scatter plots were employed for sensitivity analyses. IVW estimates suggested that serum UA levels elevated 1 unit had a potential causal association with higher odds of both cervical cancer (CC) (OR=1.147, 95% CI: 1.020-1.290) and invasive mucinous ovarian cancer (IMOC) (OR=1.199, 95% CI: 1.033-1.393). Also, endometrial carcinoma (EC) had a potential causal association with it (OR=1.012, 95% CI: 1.000-1.024). Additionally, sensitivity analyses showed the potential causal associations between UA and CC/IMOC were relatively robust. An elevated serum UA level had potential associations with CC and IMOC, whereas patients with EC should pay attention to it in clinical practice, which may reduce the potential risk of gynecological cancers. However, further evidence is needed to clarify the true relationships between UA and gynecological cancers.

Markers of and Risk Factors for the Development and Progression of Diabetic Kidney Disease

Causal association between uric acid levels and the risk of aortic aneurysm and aortic dissection: A two-sample Mendelian randomization study

The association between serum uric acid levels and peripheral vertigo diseases, namely Benign Paroxysmal Positional Vertigo (BPPV), Meniere's Disease (MD), and Vestibular Neuritis (VN), remains a subject of controversy. This study utilises the Mendelian Randomization (MR) approach to investigate the potential link between uric acid levels and these peripheral vertigo diseases, with the goal of informing preventative measures and early intervention strategies. Datasets pertaining to uric acid levels (sample size = 343 836) and BPPV (ncase = 3834, ncontrol = 209 582), MD (ncase = 1511, ncontrol = 209 582), and VN (ncase = 1224, ncontrol = 209 582) were selected from Genome-Wide Association Studies (GWAS). Two-sample MR was employed to analyse the correlation between the exposure (uric acid levels) and outcomes (BPPV, MD, VN). The MR analysis methods encompassed Inverse Variance Weighting (IVW), MR-Egger, Simple Mode, Weighted Mode, and Weighted Median methods. The results derived from the IVW analysis were considered as the primary analytical outcomes. The findings indicated no significant correlation between uric acid levels and BPPV (IVW: OR = 1.152, 95% CI: 0.971-1.367, p = 0.103), MD (IVW: OR = 1.010, 95% CI: 0.757-1.348, p = 0.943), and VN (IVW: OR = 1.005, 95% CI: 0.744-1.358, p = 0.969). This study employed a two-sample Mendelian randomization approach to conduct an in-depth analysis of the relationship between serum uric acid levels and peripheral vestibular diseases (BPPV, MD, and VN). Our findings indicate that no significant association was found between serum uric acid levels and these diseases. The results of the study do not support the hypothesis that uric acid is an independent risk factor for these conditions.

Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. N/A.

Introduction: The relationship between uric acid (UA) levels and cardiovascular and cerebrovascular diseases (CCVD) is controversial. A two-sample Mendelian randomization (MR) study was conducted to explore the causal effects of UA levels on CCVD. Methods: Genetic variants strongly associated with UA levels were selected as instrumental variables from the Genome-Wide Association Study (GWAS) dataset. The GWAS data, sourced from the Global Urate Genetics Consortium (GUGC), comprised a sample size of 110,347 individuals. The selected CCVD outcomes included stroke, coronary artery disease (CAD), as well as atrial fibrillation and flutter. The primary analytical approach employed the inverse-variance weighted (IVW) method, supplemented by MR-Egger and weighted median as complementary methods. Sensitivity analysis was performed to test heterogeneity and pleiotropy. Results: The MR analysis results indicated a causal association between UA levels and stroke (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.000–1.003; p = 0.036), CAD (OR: 1.118; 95% CI: 1.044–1.197; p = 0.001), as well as atrial fibrillation and flutter (OR: 1.141; 95% CI: 1.037–1.256; p = 0.007). The results of MR-Egger and weighted median methods confirmed the direction of the IVW results, enhancing the robustness of the findings. No significant anomalies were detected in the sensitivity analysis. Conclusion: The MR study suggests that UA levels exert causal effects on stroke, CAD, as well as atrial fibrillation and flutter.

Previous observational studies have shown that the serum uric acid (UA) level is decreased in persons with multiple sclerosis (MS). We used the two-sample Mendelian randomization (MR) method to determine whether the serum UA level is causally associated with the risk of MS. We screened 26 single-nucleotide polymorphisms (SNPs) in association with serum UA level (p < 5 × 10–8) from a large genome-wide meta-analysis involving 110,347 individuals. The SNP outcome effects were obtained from two large international genetic studies of MS involving 38,589 individuals and 27,148 individuals. A total of 18 SNPs, including nine proxy SNPs, were included in the MR analysis. The estimate based on SNP rs12498742 that explained the largest proportion of variance showed that the odds ratio (OR) of UA (per mg/dl increase) for MS was 1.00 [95% confidence interval (CI) 0.90–1.11; p = 0.96]. The main MR analysis based on the random effects inverse variance weighted method showed that the pooled OR was 1.05 (95% CI 0.92–1.19; p = 0.50). Although there was no evidence of net horizontal pleiotropy in MR-Egger regression (p = 0.48), excessive heterogeneity was found via Cochran’s Q statistic (p = 9.6 × 10–4). The heterogeneity showed a substantial decrease after exclusion of two outlier SNPs (p = 0.17). The pooled ORs for the other MR methods ranged from 0.89 (95% CI 0.65–1.20; p = 0.45) to 1.05 (95% CI 0.96–1.14; p = 0.29). The results of sensitivity analyses and additional analyses all showed similar pooled estimates. MR analyses by using 81 MS -associated SNPs as instrumental variables showed that genetically predicted risk of MS was not significantly associated with serum UA level. The pooled OR was 1.00 (95% CI 0.99–1.02; p = 0.74) for the main MR analysis. This MR study does not support a causal effect of genetically determined serum UA level on the risk of MS, nor does it support a causal effect of genetically determined risk of MS on serum UA level.

The importance and function of serum uric acid (UA) levels in patients with cardiovascular disease or stroke are unclear. We sought to evaluate the appropriate UA levels for stroke patients and the association between endogenous UA levels and clinical outcomes in acute ischemic stroke (AIS) patients, particularly regarding the possible interaction between gender and UA levels with respect to AIS prognosis. We examined 303 patients who had an onset of ischemic stroke within 48 h. Of those, 101 patients received thrombolytic treatment. Serum UA (μmol/L) levels were measured the second morning after admission. Patient prognosis was evaluated 90 days after clinical onset by modified Rankin Scale. Patients were divided into four groups according to serum UA quartiles. A binary multivariate logistic regression model was used to assess clinical relevance in regard to functional outcome and endogenous UA levels. Analysis of subgroups by gender and normal glomerular filtration rate were also been done. Poor functional outcome was associated with older age, history of atrial fibrillation, or higher baseline National Institutes of Health Stroke Scale scores. After adjustment for potential confounders, patients with higher UA levels (>380 μmol/L) or lower UA levels (≤250 μmol/L) were 2-3 times more likely to have a poor outcome (OR 2.95, 95% CI 1.14-7.61; OR 2.78, 95% CI 1.02-7.58, respectively) compared to the baseline group (UA level 316-380 μmol/L). The same results were observed in thrombolyzed patients. Patients with high and low UA levels were 9-18 times more likely to having poor outcomes compared to the baseline group (UA level: 316-380 μmol/L; OR 18.50, 95% CI: 2.041-167.67; OR 9.66, 95% CI 1.42-65.88, respectively). In men, patients with high UA levels were 6 times more likely to have poor outcomes compared to the baseline group (UA level: 279-334 μmol/L; OR 6.10, 95% CI 1.62-22.93). However, female patients with UA level 271-337 μmol/L were seven times more likely to perform badly compared to the baseline group (UA level >337 μmol/L, OR 7.06, 95% CI 1.00-49.81). Serum UA levels in an appropriate range were associated with better outcome in patients with AIS but may be harmful when too high or too low. The association of UA levels with AIS prognosis differed in male and female patients, which highlights the necessity of stratifying by gender in investigations of cerebrovascular risk factors.

Association between uric acid and risk of venous thromboembolism in East Asian populations: a cohort and Mendelian randomization study

PurposeAlthough increasing lines of evidence showed associations between serum uric acid (UA) levels and schizophrenia, the causality and the direction of the associations remain uncertain. Thus, we aimed to assess whether the relationships between serum UA levels and schizophrenia are causal and to determine the direction of the association.Patients and MethodsTwo-sample bidirectional Mendelian randomization (MR) analyses and various sensitivity analyses were performed utilizing the summary data from genome-wide association studies within the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium. Secondary MR analyses in both directions were conducted within summary data using genetic risk scores (GRSs) as instrumental variables.ResultsThree MR methods provided no causal relationship between serum UA and schizophrenia. Furthermore, GRS approach showed similar results in the three MR methods after adjustment for heterogeneity. By contrast, inverse variance weighted method, weighted median and GRS approach suggested a causal effect of schizophrenia risk on serum UA after adjustment for heterogeneity (per 10-symmetric percentage increase in schizophrenia risk, beta: −0.039, standard error (SE): 0.013, P = 0.003; beta: −0.036, SE: 0.018, P = 0.043; beta: −0.039, SE: 0.013, P = 0.002; respectively). Moreover, in both directions’ analyses, the heterogeneity and sensitivity tests suggested no strong evidence of bias due to pleiotropy.ConclusionSchizophrenia may causally affect serum UA levels, whereas the causal role of serum UA concentrations in schizophrenia was not supported by our MR analyses. These findings suggest that UA may be a useful potential biomarker for monitoring treatment or diagnosis of schizophrenia rather than a therapeutic target for schizophrenia.

Background: Elevated serum uric acid (UA) levels are associated with adverse outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). However, the relation between UA and acute kidney injury (AKI) in this population is unclear. We evaluated the effect of elevated UA levels on the risk to develop AKI among consecutive STEMI patients treated with primary PCI. Methods: We performed a retrospective analysis of 1,372 consecutive patients admitted with the diagnosis of STEMI between January 2008 and February 2015. Patients were stratified into quartiles according to UA levels as follows: quartile 1, <4.7 mg/dl; quartile 2, 4.8 to <5.6 mg/dl; quartile 3, 5.7 to <6.6 mg/dl, and quartile 4, >6.7 mg/dl. Results: STEMI patients with elevated UA levels had a higher frequency of AKI (4 vs. 6% vs. 10 vs. 24%; p < 0.001). In a subgroup analysis of patients with reduced baseline estimated glomerular filtration rate (≤60 ml/min/1.73 m²), an elevated UA level was associated with a significant risk to develop AKI, with 46% of patients developing AKI in the highest UA quartile. In a multivariate logistic regression model, for every 1-mg/dl increase in the UA concentration, the adjusted risk for AKI increased by 46% (OR = 1.46, 95% CI 1.18-1.66; p < 0.001). Conclusions: Among STEMI patients undergoing primary PCI, elevated UA levels are an independent predictor of AKI.

Objective To investigate the relation between serum uric acid ( UA ) levels and ischaemic stroke.Methods 78 patients with ischaemic stroke were assigned to the study group and 80 healthy people were enrolled as control.Serum UA levels were compared between the two group.The association of UA with disease serverity and prognosis in patients was analyzed.Results UA levels were significantly higher in the study group than in the control group ( [375.93 ± 42.67]mol/L vs.[260.43 ±24.78]mol/L,P＜ 0.01 ).Serum UA levels increased gradually in all the patients with slight,moderate,or severe ischemic stroke ( P＜ 0.05 for all comparisons ).The number of the patients who were not cured or were dead was greater in the patients with an elevated UA level than in those with a normal UA level( P＜ 0.05 ).Conclusions Serum uric acid level was closely associated with the disease severity and prognosis in patients with ischemic stroke. Key words: Ischemic stroke; Uric acid

A plethora of studies have demonstrated that the level of uric acid (UA) and gout are the risk factors for erectile dysfunction (ED). However, the causal effect of UA level and gout on ED is still unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between ED and UA levels as well as gout. We performed a bidirectional MR analysis using summary statistics from genome-wide association studies (GWAS) to investigate the causal association between ED and UA levels as well as gout. We meticulously selected single nucleotide polymorphisms (SNPs) based on rigorous criteria as instrumental variables. Four two-sample MR analysis methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode, were applied in our study. Furthermore, several sensitivity analyses including Cochrane's Q-test, MR-Egger intercept test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) global test, and leave-one-out analysis were performed to assess heterogeneity, horizontal pleiotropy, and stability. The study included one dataset related to UA levels (GWAS meta-analysis conducted by Tin et al.), two datasets related to gout (ukb-b-12765 and finn-R9-M13_GOUT), and one dataset related to ED (GWAS meta-analysis conducted by Bovijn et al.). MR results of the IVW method indicated that UA levels and gout were not causally associated with ED in three UA levels/gout-related datasets (IVW, odds ratios (OR): 0.99, 95% confidence interval (CI): 0.92-1.07, p = 0.834; 3.20, 0.17-61.69, 0.441; 1.03, 0.97-1.09, 0.372, respectively). The reverse MR revealed no evidence of a causal effect of ED on UA levels or gout according to the IVW method (OR: 0.99, 95% CI: 0.96-1.02, p: 0.568; 1.00, 1.00-1.00, 0.555; 0.97, 0.89-1.05, 0.425, respectively). The results of other MR analysis methods were consistent with IVW. Furthermore, sensitivity analysis suggested that the results were robust, with no pleiotropy or heterogeneity detected. Our MR study supports no bidirectional causal effect of UA level or gout on ED.

Previous findings on the association between uric acid (UA) levels and cancer risk are conflicting. Moreover, the mechanisms underlying the interactions between UA levels, fatty acid traits, and cancer outcomes remain complex; it is still unclear whether elevated UA levels influence fatty acid traits and, thereby, contribute to an increased cancer risk. Therefore, we aimed to investigate the association between UA levels and cancer risk, with a specific focus on the potential mediating role of fatty acid traits. We employed a Mendelian randomization (MR) analysis utilizing genetic data from large-scale genome-wide association studies to assess the causal relationships among UA levels, fatty acid traits, and cancer risk. The primary method used was the inverse variance-weighted approach alongside Bayesian-weighted Mendelian randomization. Other MR models were also applied for comparison. Sensitivity analyses, based on various statistical assumptions, were also performed to evaluate the robustness of the findings. A two-step MR analysis was conducted to explore the mediating effects of fatty acid traits on the relationship between UA levels and cancer risk. Elevated UA levels were associated with an increased risk of in situ neoplasms, cervical cancer, and invasive mucinous ovarian cancer, while they were linked to a decreased risk of cancers of the eye and adnexa, small cell lung cancer, bronchus and lung cancer, respiratory system and intrathoracic organ cancers, as well as lung cancer. Mediation analysis revealed that fatty acid traits, particularly the docosahexaenoic acid/trans fatty acid ratio, mediated the relationship between UA levels and lung cancer risk. These findings underscore the potential of fatty acid traits to mediate the association between UA levels and cancer risk, offering new insights for targeted interventions and potentially improving clinical outcomes.

Background: Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. High-sensitivity Troponin I (Hs-TnI) is a key biomarker for early diagnosis of myocardial injury. Recent studies also suggest a possible link between elevated serum uric acid levels and cardiovascular events. This study aims to evaluate the levels of Hs-TnI and uric acid in patients presenting with myocardial infarction and assess their potential clinical correlation. Aim and Objectives: To assess serum Hs-Troponin I and uric acid levels in patients diagnosed with AMI and determine their relationship with severity and clinical profile. Materials and Methods: This hospital-based cross-sectional observational study was conducted over a 12-month period from April 2024 to March 2025 at the Department of Biochemistry, NMCH, Jamuhar, Sasaram. A total of 150 AMI patients were included. Serum Hs-TnI and uric acid levels were measured using chemiluminescence immunoassay and enzymatic methods respectively. Data were statistically analyzed for correlation with clinical parameters and risk factors. Results: A significant elevation in serum Hs-TnI and uric acid levels was observed in all AMI patients. Hs-TnI levels were markedly higher in STEMI patients compared to NSTEMI. Elevated uric acid levels were more prevalent in patients with a history of hypertension and metabolic syndrome. A positive correlation was found between uric acid levels and severity of myocardial infarction, as evidenced by ECG and echocardiography findings. Conclusion: Hs-Troponin I remains a sensitive and specific biomarker for AMI diagnosis. Elevated uric acid levels may serve as an adjunct marker indicating increased cardiovascular risk and worse outcomes in myocardial infarction. Dual assessment of Hs-TnI and uric acid may enhance early risk stratification and guide therapeutic decisions.