Publications by authors named "H K Ea"
Article Synopsis
- - Gout is a chronic condition caused by the immune system's reaction to monosodium urate crystals due to high uric acid levels, and recent research sheds light on its inflammatory mechanisms.
- - A large genome-wide association study (GWAS) involving 2.6 million people identified 377 genetic locations linked to gout, with a focus on 149 new loci related to urate and gout inflammation.
- - The study also pinpointed candidate genes influencing the inflammatory response in gout, including those affecting NLRP3 inflammasome activity, and suggests a potential causal role of specific genetic factors in developing the disease.
Article Synopsis
- Monosodium urate (MSU) and calcium pyrophosphate (CPP) micro-crystals lead to inflammation in conditions like gout and chondrocalcinosis by activating macrophages, which release cytokines like IL-1β.
- The maturation of IL-1β is driven by the NLRP3 inflammasome, which gets activated in response to these crystals.
- This activation is dependent on the LRRC8 anion channels, as they help regulate cell volume and trigger ATP release, resulting in IL-1β maturation and inflammation, demonstrating their important role in joint inflammation from crystal deposits.
Objective: Our objective was to prospectively investigate prediagnostic population-based metabolome for risk of hospitalized gout (ie, most accurate, severe, and costly cases), accounting for serum urate.
Methods: We conducted prediagnostic metabolome-wide analyses among 249,677 UK Biobank participants with nuclear magnetic resonance metabolomic profiling (N = 168 metabolites, including eight amino acids) from baseline blood samples (2006-2010) without a history of gout. We calculated multivariable hazard ratios (HRs) for hospitalized incident gout, before and after adjusting for serum urate levels; we included patients with nonhospitalized incident gout in a sensitivity analysis.
Objectives: Inflammatory mediators such as interleukin 6 (IL-6) are known to activate catabolic responses in chondrocytes during osteoarthritis (OA). This study aimed to investigate the role of a downstream target gene of IL-6, the serine protease inhibitor SerpinA3N, in the development of cartilage damage in OA.
Methods: RNA sequencing was performed in murine primary chondrocytes treated with IL-6, and identified target genes were confirmed in human and murine OA cartilage samples.