title: Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children.
abstract: OBJECTIVE
  Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry.
  
  
  METHODS
  Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated.
  
  
  RESULTS
  Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history.
  
  
  CONCLUSIONS
  Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.
authors: Department of Pediatrics, Hacettepe University, , Ankara, Turkey.
authors: Seza
authors: S
authors: Ozen
authors: Erkan
authors: E
authors: Demirkaya
authors: Gayane
authors: G
authors: Amaryan
authors: Isabelle
authors: I
authors: Koné-Paut
authors: Adem
authors: A
authors: Polat
authors: Pat
authors: P
authors: Woo
authors: Yosef
authors: Y
authors: Uziel
authors: Consuelo
authors: C
authors: Modesto
authors: Martina
authors: M
authors: Finetti
authors: Pierre
authors: P
authors: Quartier
authors: Efimia
authors: E
authors: Papadopoulou-Alataki
authors: Sulaiman M
authors: SM
authors: Al-Mayouf
authors: Giovanna
authors: G
authors: Fabio
authors: Romina
authors: R
authors: Gallizzi
authors: Luca
authors: L
authors: Cantarini
authors: Joost
authors: J
authors: Frenkel
authors: Susan
authors: S
authors: Nielsen
authors: Michael
authors: M
authors: Hofer
authors: Antonella
authors: A
authors: Insalaco
authors: C
authors: C
authors: Acikel
authors: Huri
authors: H
authors: Ozdogan
authors: Alberto
authors: A
authors: Martini
authors: Nicolino
authors: N
authors: Ruperto
authors: Marco
authors: M
authors: Gattorno
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D010505:Familial Mediterranean Fever / Q000208:ethnology / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D008877:Middle East / Q000453:epidemiology / Q000208:ethnology; D009154:Mutation; D010641:Phenotype; D000071198:Pyrin; D012042:Registries; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin
keywords: Epidemiology; Familial Mediterranean Fever; Gene Polymorphism