title: Can genetics aggravate the health of isolated and remote populations? The case of gout, hyperuricaemia and osteoarthritis in Dalmatia.
abstract: BACKGROUND
  The aim of this study was to investigate whether genetics may be considered an additional risk factor for health in isolated and remote populations, compared with their populations of origin. In this study, two remote island population samples from Croatia (from the islands of Vis and the Korcula) were compared with mainland controls from the coastal city of Split. The analyses focused on gout, hyperuricaemia and osteoarthritis, as examples of complex, multifactorial diseases.
  
  
  METHODS
  A total of 3006 examinees from all three sites in Dalmatia, Croatia were included in the descriptive part of the study, within a large-scale project of 10,001 Dalmatians. Additionally, a subset of 2428 subjects was genotyped and information on three genomic loci was used in this study. All three loci belong to SLC2A9 gene, considered to have a major role in the regulation of serum uric acid concentration (rs6449213, rs1014290 and rs737267).
  
  
  RESULTS
  There was a much a higher prevalence of gout in the isolated populations compared with the mainland sample (3.3% in Vis, 2.2% in Korcula and 1.7% in Split, after age standardization). Furthermore, standardized prevalence of hyperuricaemia (defined as serum uric acid ≥403 mmol/L) was 9.9% in Vis, 5.6% in Korcula and 6.1% in Split. Analysis of the allele frequencies for the three loci of SLC2A9 suggested that in all three instances the prevalence of deleterious genotypes was highest in Vis, followed by Korcula, which had higher or comparable prevalence to the city of Split. Multivariate analysis, adjusted for the main confounder effects indicated that those on the island of Vis, which has the higher degree of isolation, had significantly higher odds ratio for both hyperuricaemia (odds ratio 1.90 95% confidence intervals [1.36-2.64]) and osteoarthritis, but not gout (3.37 [2.14-5.32]). The difference between Split and Korcula included only greater odds for osteoarthritis (1.92 [1.20-3.06]).
  
  
  CONCLUSIONS
  Isolated and remote populations that maintain a sufficient level of genetic isolation may suffer not only from consequences of geographic and social isolation, but their population genetic structure may also further contribute to poorer health status and outcomes.
authors.affiliation: Medical School, University of Split, Split, Croatia. ana.miljkovic@mefst.hr
authors.forename: Ana
authors.initials: A
authors.lastname: Miljković
authors.forename: Marina
authors.initials: M
authors.lastname: Pehlić
authors.forename: Danijela
authors.initials: D
authors.lastname: Budimir
authors.forename: Grgo
authors.initials: G
authors.lastname: Gunjača
authors.forename: Ivana
authors.initials: I
authors.lastname: Mudnić
authors.forename: Arsen
authors.initials: A
authors.lastname: Pavić
authors.forename: Iris
authors.initials: I
authors.lastname: Jerončić
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolčić
authors.forename: Mladen
authors.initials: M
authors.lastname: Boban
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Ozren
authors.initials: O
authors.lastname: Polašek
mesh_terms: D017523:Croatia / Q000453:epidemiology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006073:Gout / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D010003:Osteoarthritis / Q000453:epidemiology / Q000235:genetics*; D012424:Rural Population; D012934:Social Isolation
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human