Gout Urate Cryst. Depos. Dis., Volume 3, Issue 2 (June 2025) – 4 articles

Background: Mendelian randomization (MR) is a genetic epidemiological method used to infer causal relationships between exposures and outcomes. Its application in hyperuricemia and gout has grown exponentially owing to the ready availability of summary statistics from genome-wide association studies and the ease of applying the two-sample MR technique. However, indications of poor study quality suggest the need for systematic evaluation. Objective: This study evaluated the quality of two-sample MR studies on hyperuricemia and gout and developed a scoring system to help reviewers and readers assess their quality and validity. Methods: A systematic review was conducted on 86 two-sample MR studies published between 2016 and 2024. Studies were assessed using a scoring system encompassing study design, statistical methods, result interpretation, and adherence to STROBE-MR guidelines. Scores could range between −9 and 21. Trends in quality over time were analyzed using regression models. Results: Study quality scores ranged from 0 to 19, with a mean of 9.1 and median of 11, demonstrating wide variability. High-quality studies adhered to MR assumptions, used independent datasets, and conducted replication analyses, while lower-quality studies often failed to correct the p-value when needed, test for confounders, address dataset overlap, or report study power. Despite the increased publication of MR studies, overall quality has not improved over time. Conclusion: There is variability in two-sample MR study quality. Our proposed scoring system offers a practical framework for evaluating MR studies, aiding researchers and clinicians in identifying robust findings while promoting higher methodological standards. Full article

Monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals are the most common types of crystals found in the joints. Each type of crystal has been associated with the onset of different joint diseases. However, the mechanisms identified for one type of crystal are often generalized to the others; thus, overlooking the specific and distinct molecular and cellular responses activated by each type of crystal. This review describes the similarities and differences of the main molecules and mechanisms underlying the diseases associated with the three different types of crystals. Specifically, current knowledge on crystal properties and formation, on the induction and resolution of inflammation, on mechanisms involved in pain processing and senescence, and on the role of mitochondria and genomic instability are elucidated. A more complete and detailed study of the specific molecular mechanisms induced by different crystals is necessary to advance our understanding of the pathogenesis and to help identify innovative opportunities for prevention and treatment of crystal deposition disease. Full article

Genetic association studies in gout have identified genetic variants in or near genes involved in the biosynthesis and transport of urate and in immunological pathways. However, the causal role of the remaining genetic variants, genes, and pathways in gout is not clear. Here, we present the results from a genetic colocalization analysis of gout-associated signals with metabolite quantitative trait loci (mQTL), shedding light on the metabolites that are likely directly affected by genetic variants associated with gout. We identified 141 candidate metabolites with evidence of colocalization with at least one gout-associated genetic signal, of which 29 showed evidence of a causal relationship with gout by Mendelian randomization. Among the 29 metabolites were lysophosphatidylcholines, which may affect the inflammatory response by binding to the TLR-2/4 receptors, providing plausible candidate metabolites for future studies that link metabolites with inflammatory processes in gout. Full article

Calcium pyrophosphate deposition disease (CPPD) has been shown to be associated with inflammatory arthritis such as rheumatoid arthritis. However, few studies have investigated the correlation between CPPD and psoriatic arthritis (PsA). Our study aimed to determine whether there were higher rates of PsA in patients with CPPD than controls. A retrospective cohort study was conducted using the Veterans Affairs’ Corporate Data Warehouse. Individuals with a CPPD ICD code were matched with controls and diagnoses of PsA and psoriasis were collected. A total of 41,084 CPPD patients were matched with 119,192 controls. The proportion of CPPD patients with PsA diagnosis was more than double that of controls (1.07% vs. 0.37%; p < 0.0001), and more CPPD patients were diagnosed with psoriasis (3.05% vs. 2.52%; p < 0.0001). Those with CPPD had higher odds of a PsA diagnosis (OR 3.550, 95% CI 2.602–4.844). A total of 61.59% of PsA diagnoses preceded the CPPD diagnoses by at least one year. This is the first case–control study demonstrating an association between CPPD and PsA, potentially related to the fact that both PsA and CPPD could be triggered by trauma, and are closely associated with osteoarthritis. It also is possible that inflammatory pathways contribute to CPP crystal deposition in joints. Full article