From Hyperuricaemia to Gout—Inflammatory Pathways
Gout is a common form of inflammatory arthritis that affects approximately 1 to 2% of the population in developed countries. In New Zealand, the prevalence of gout is particularly high (~4%) with Māori and Pacific Islanders being most affected (6 and 8%, respectively). Gout is caused by the deposition of monosodium urate (MSU) crystals in the joints and other tissues due to chronic elevation of urate levels (hyperuricaemia) in the blood. Although hyperuricaemia is considered a key regulator for development of gout, however, not all people with hyperuricaemia develop gout. This indicates other factors are also required to initiate the inflammatory response to MSU crystals. The primary mechanism of inflammation in gout involves the ingestion of MSU crystals by resident immune cells (primarily macrophages) causing the activation of the NOD-like receptor family, pyrin containing domain 3 (NLRP3) inflammasome, which in turn releases IL-1β and other inflammatory mediators to enhance the inflammatory response. Genome-wide association studies have discovered various susceptible loci that influence serum urate levels. However, the genetic contribution to the progression from hyperuricaemia to gout is not well understood. Genes that encode proteins within the NLRP3 complex have also been associated with gout risk, however, this area of research lacks large-scale studies. Furthermore, the inflammatory response in gout is not an outcome of a single process rather integration of various mechanisms such as autophagy, mitochondrial processes, which leads to the initiation and amplification of inflammatory reactions. Therefore, variations in genes relevant to these mechanisms could confer gout risk. This study aims to explore the genetic contribution of such inflammatory loci in developing gout.
| Date | Tuesday, 27 November 2018 |
|---|---|
| Time | 12:00pm - 1:00pm |
| Audience | All University |
| Event Category | Health Sciences |
| Event Type |
Departmental Seminar |
| Campus | Dunedin |
| Department | Biochemistry |
| Location | Biochemistry Seminar Room 231 |
