TOPATA: Epidemiology of Gout in French Polynesia
Study Details
Study Description
Brief Summary
Gout is a chronic disease caused by the deposit of monosodium urate (MSU) crystals in body tissues secondary to hyperuricemia. Patients with gout suffer severe attacks of acute joint pain. As the disease progresses, the joint pain becomes chronic and associated with disabling and deformative manifestations called tophi. Gout is strongly associated with various comorbidities including cardiovascular disease and chronic kidney failure. Gout is a very common disease, affecting 0.9% of the adult population in France and nearly 4% of the North-American population. Data from New Zealand show a particularly high prevalence of gout among Polynesians (minority populations in New Zealand and other islands of the South Pacific) that would be explained by genetic susceptibility and frequently intertwined with metabolic diseases. Recent findings obtained from the Polynesian population in New Caledonia disclose high prevalence figures close to 7%, a level expected to be confirmed by an epidemiology study that will be conducted in parallel with the present study and designed to determine the precise prevalence of gout in French Polynesia and the most frequently associated genetic variants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
International genomic studies conducted in populations with hyperuricemia and gout have identified a number of associated alleles. The strength of the association between a given allele and gout (or hyperuricemia) provides an indication of the importance of the encoded protein in disease pathogenesis. It was in this way that the development of gout was found to depend on renal urate transporters that were subsequently targeted by new uricosuric therapies.
Overall, the search for gout-associated genes has mostly been done in the general European population and revealed a small number of candidate loci. Most of these only contribute a small amount to the heritability for gout susceptibility, suggesting that additional genes and mechanisms of genetic influence are yet to be discovered. A common feature of Genome-Wide Association studies done so far is that usually large sample sizes are required in order to detect differences in allele frequencies and their contribution to different traits between test groups. The Polynesian population of French Polynesia possesses characteristics that make it particularly attractive to carry out population-based genetic research. Historical records indicate that the Polynesians of Tahiti and surrounding islands originate from a small founder population that has undergone a number of bottlenecks, eventually becoming a genetically homogenous population with a fairly high degree of consanguinity. The combination of a historic founder event, continued isolation and recent expansion are all ideal properties for a Genome Wide Association Study, as they ensure that 1) population stratification will be easy to correct when performing association tests and 2) there are likely high-effect variants that were kept at low frequency in mainland Europe due to negative selection but rose to high frequencies in the Polynesians via the increase in genetic drift or selection through adaptation to a specific environment and diet. Therefore, it is plausible that rare variants with large effect on health-related quantitative traits may be more easily detectable in Polynesians, even with much smaller sample sizes.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Epidemiological study
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Other: Epidemiological study
Questionnaires (quality of life, gout, life habit, comorbidities) anthropometrics and health measures DNA analysis RNA analysis Metabolomic analysis
|
Outcome Measures
Primary Outcome Measures
- Gout Prevalence [6 months]
Measure of gout prevalence
Secondary Outcome Measures
- Diagnosis of Hyperuricemia [6 months]
Diagnosed when uricemia is higher than 360 µmol/l
- Genome wide analysis for identification of genetic variants linked to gout [6 months]
Analysis of the genetic determinants of gout and hyperuricemia in French Polynesia via a pan-genomic analysis using complete and then rapid sequencing techniques
- HLA B58:01 allele prevalence [6 months]
- Multiple correlation between renal failure, diabetes, gout and cardiovascular comorbidities [6 months]
The association between cardiovascular comorbidities/renal failure/diabetes and gout will be investigated using a multivariate logistic regression model.
- Multiple correlation between renal failure, diabetes, hyperuricemia and cardiovascular comorbidities [6 months]
The association between cardiovascular comorbidities/renal failure/diabetes and hyperuricemia will be investigated using a multivariate logistic regression model.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Living in Tahiti, Moorea, Tahaa-Raiatea, Tikehau, Nuku Hiva, Mangareva, Rurutu
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Agreeing to participate in the study
Exclusion Criteria:
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Homeless
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Living in communities (military camp, hospices, university residence, ...)
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Unable to answer questionnaires
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Under guardianship
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre Hospitalier de la Polynésie Française | Pirae | French Polynesia | 98713 |
Sponsors and Collaborators
- Lille Catholic University
- Variant Bio, Inc.
- University of Birmingham
- University of San Diego
- Ministry of Health, French Polynesia
Investigators
- Principal Investigator: Tristan Pascart, MD, PhD, GHICL
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RC-P00104