ArticleScientific reports2024
Effects of uric acid on ischemic diseases, stratified by lipid levels: a drug-target, nonlinear Mendelian randomization study.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Exploring the relationship between XDH gene variants and serum urate and xanthine dehydrogenase levels in gout.Clinical rheumatology · 2026Article
- Increased Xanthine Oxidoreductase Activity in Patients With Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.CHEST pulmonary · 2026Article
- Mendelian Randomization Studies: A Metric for Quality Evaluation.Gout, urate, and crystal deposition disease · 2025Article
- Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Managing Gout in Patients with Metabolic Syndrome.Drugs & aging · 2024Review
- The interplay between cytokines and stroke: a bi-directional Mendelian randomization study.Scientific reports · 2024Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78-0.93; P < 0.001), cerebral infarction (OR, 0.86; 95% CI, 0.75-0.98; P = 0.023), AMI (OR, 0.79; 95% CI, 0.66-0.94; P = 0.010) in individuals with triglycerides ≥ 188.00 mg/dL, and cerebral infarction in individuals with low-density lipoprotein cholesterol (LDL-C) ≤ 112.30 mg/dL (OR, 0.76; 95% CI, 0.61-0.96; P = 0.020) or LDL-C of 136.90-157.40 mg/dL (OR, 0.67; 95% CI, 0.49-0.92; P = 0.012). XDH-variant-induced uric acid reduction lowers the risk of gout, AMI for individuals with high triglycerides, and cerebral infarction except for individuals with high LDL-C, highlighting the potential heterogeneity in the protective effects of xanthine oxidase inhibitors for treating AMI and cerebral infarction depending on the lipid profiles.
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