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

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22 pages, 2757 KiB  
Review
Comparison of Pathophysiological Mechanisms Among Crystal-Induced Arthropathies
by Maddalena Zangari, Roberto Luisetto, Roberto Pilot, Paola Contessa, Raffaella Signorini, Stefano Masiero and Anna Scanu
Gout Urate Cryst. Depos. Dis. 2025, 3(2), 7; https://doi.org/10.3390/gucdd3020007 - 10 Apr 2025
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Abstract
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 [...] Read more.
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
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15 pages, 12009 KiB  
Article
Colocalization Analysis Reveals Shared Genetic Loci Contributing to Gout and Metabolite Levels
by Riku Takei, Nicholas A. Sumpter, Megan P. Leask and Tony R. Merriman
Gout Urate Cryst. Depos. Dis. 2025, 3(2), 6; https://doi.org/10.3390/gucdd3020006 - 27 Mar 2025
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Abstract
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, [...] Read more.
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
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6 pages, 291 KiB  
Article
Higher Rates of Psoriatic Arthritis in Patients with Calcium Pyrophosphate Deposition Disease than in Controls: A Retrospective Cohort Study
by Natalie Anumolu, Ann Rosenthal, Katherine Sherman and Shikha Singla
Gout Urate Cryst. Depos. Dis. 2025, 3(2), 5; https://doi.org/10.3390/gucdd3020005 - 27 Mar 2025
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Abstract
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 [...] Read more.
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
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