FENUA-METABOGOUT : Genetic Landscape of Gout, Inflammation and Metabolic Diseases in French Polynesia.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 2,750
- 试验地点
- 6
- 主要终点
- GWAS-identified associations between population-enriched genetic variants and health-related traits
研究概览
简要总结
The aim of this research is to characterise the genetic and molecular landscape of gout, inflammation and metabolic diseases, as well as the associated molecular, anthropomorphic and pathological characteristics.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All participants:
- •Age between 18 and 75 years old inclusive
- •Signature of informed consent
- •Fasting for the collection of biological samples
- •Declared Polynesian ancestry
- •Affiliated to a social security scheme
- •General population group :
- •Not having participated to the 2021 TOPATA study
- •Visiting a general practitioner (for whatever reason)
- •Gout Group :
- •Managed at the rheumatology clinic of the Taaone Hospital Centre (CHT) in Papeete by Dr Baptiste Gérard.
- •Tophaceous gout sub-group:
- •Present with tophaceous gout.
- •Gout crisis subgroup:
- •Be within 48 hours of the onset of a gout attack
- •Agree to return 1 week after inclusion for the second blood and urine sample.
- •2021 follow-up group:
- •To have been included in the TOPATA study in 2021
- •Have taken the genetic and biological samples that generated the genetic and serum urate data for the 2021 study
- •Have hyperuricaemia without signs of gout OR without hyperuricaemia or gout at the time of inclusion in TOPATA
排除标准
- •All participants :
- •Refusal or inability to understand or give consent
- •Physical inability to follow and respect the protocol
- •1st degree relative*,
- •Person under guardianship or trusteeship
- •Pregnant or breast-feeding woman
- •* If several relatives from the same household are eligible to participate, only one person may be included in the study. The choice is left to the discretion of the investigator or the first person met. However, both members of a couple (e.g. husband and wife) may participate.
- •General population group :
- •Unable to return for sampling if required.
- •Gout group :
- •Person wearing a knee prosthesis
- •People suffering from other inflammatory rheumatic diseases
结局指标
主要结局
GWAS-identified associations between population-enriched genetic variants and health-related traits
时间窗: 12 month
Effect estimates (odds ratios or beta coefficients) for statistically significant associations between population-enriched genetic variants and predefined health-related traits identified through GWAS.
次要结局
- Multiple correlation between gout, hyperuricemia, type 2 diabetes and obesity(12 month)
- Incidence rate of gout or HU in French Polynesia between 2021 and 2025(4 years)
- Proportion of each type of urate-lowering therapy prescribed annually between 2019 and 2025(4 years)
- Incidence of major adverse cardiovascular events (MACE) in patients with gout, diabetes, or obesity(12 month)
- Determinants of progression from asymptomatic hyperuricemia (in 2021) to gout (in 2025)(4 years)
- Multiple correlation between metabolic changes and disease evolution(12 month)
- Multiple correlation between molecular, clinical features and gout severity(12 month)
- Multiple correlation between gout attacks, clinical manifestations, gene expression, proteomic, and metabolomic profiles.(12 month)
- Change in clinical and molecular characteristics of acute gout flares between baseline and 1-week visit(one week)