Landscape of Gout in French Polynesia.

Recent work by the GHICL has highlighted the imminent public health problem represented by gout and hyperuricaemia in French Polynesia, with gout affecting around 15% and hyperuricaemia 71.6% of the adult population.

Hyperuricaemia is defined as a serum urate level above the saturation point, leading to its crystallisation under biological conditions. It is generally accepted that hyperuricaemia (HU) begins at 6.0 mg/dL (360 µmol/L).

The best-known consequence of hyperuricaemia is the development of gout, which results from the inflammatory response to the presence of monosodium urate (MSU) crystals in and around the joints. The factors modulating the deposition of MSU crystals in HU are poorly understood and a potential genetic contribution is unknown. It is known that the inflammatory response to the presence of MSU crystal deposits causing gout flares is mediated by activation of the NLRP33 inflammasome, but there is significant variability in this inflammatory response within the same individual (irregular recurrence of flares), and between individuals. The exceptionally high prevalence of HU that have been identified in French Polynesia represents a major health burden, as hyperuricaemia and gout are associated with many other cardiometabolic diseases.

For example, hyperuricaemia, BMI and type 2 diabetes are all associated with the risk of gout. The association between gout and cardiovascular events is also well known, and is thought to be mediated by a persistent inflammatory state. These data are particularly relevant in the context of French Polynesia where, in addition to high rates of gout and HU, a prevalence of obesity of over 40% (BMI \>30kg/m2) and a prevalence of diabetes (based on HBA1c measurements) of over 13% was previously identified by the same team.

This last point is particularly striking as the prevalence of diabetes based on self-reported diagnosis was only 7%, indicating that many people are probably undiagnosed and therefore untreated. A better understanding not only of the mechanism and causal link between these conditions and risk factors, but also of the genetic basis of the disease, could lead to the development of therapies and to the improvement in diagnosis. This is particularly crucial in French Polynesia, where hyperuricaemia and its pathological effects on cardiometabolic health affect a large proportion of the adult population.

Here a multi-pronged approach to take advantage of a previous study named 'TOPATA' (NCT04812886) performed previously in French Polynesia, is proposed. The idea is to expand the existing cohort, in order to identify the genetic effectors contributing to the high rates of metabolic diseases previously observed, and to track the longitudinal impacts of HU.

• Multiple correlation between gout, hyperuricemia, type 2 diabetes and obesity [Time frame: 12 month]
• Incidence rate of gout or HU in French Polynesia between 2021 and 2025 [Time frame: 4 years]
• Proportion of each type of urate-lowering therapy prescribed annually between 2019 and 2025 [Time frame: 4 years]
• Incidence of major adverse cardiovascular events (MACE) in patients with gout, diabetes, or obesity [Time frame: 12 month]
• Determinants of progression from asymptomatic hyperuricemia (in 2021) to gout (in 2025) [Time frame: 4 years]
• Multiple correlation between metabolic changes and disease evolution [Time frame: 12 month]
• Multiple correlation between molecular, clinical features and gout severity [Time frame: 12 month]
• Multiple correlation between gout attacks, clinical manifestations, gene expression, proteomic, and metabolomic profiles. [Time frame: 12 month]
• Change in clinical and molecular characteristics of acute gout flares between baseline and 1-week visit [Time frame: one week]