title: A variant allele of the Mediterranean-fever gene increases the severity of gout.
abstract: BACKGROUND
  Gout is a clinical syndrome that occurs as an inflammatory response to increased concentration of uric acid and monosodium urate crystals. Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease with autosomal recessive inheritance. The Mediterranean fever (MEFV) gene is responsible for FMF and encodes pyrin that suppresses the inflammatory response. Most of the FMF-related mutations have been identified in exon 2 (e.g., E148Q and R202Q) and exon 10 (M680I, M694V, M694I and V726A) of the MEFV gene, and each missense mutation is known to increase production of interleukin-1, a proinflammatory cytokine. Our aim was to investigate effects of MEFV variant alleles on the manifestations of gout.
  
  
  METHODS
  Seventy-one patients diagnosed with gout (age: 61.73 ± 11.73 years, F/M: 14/57) and 50 healthy subjects (age: 61.48 ± 11.97, F/M: 10/40) as controls were included in this study.
  
  
  RESULTS
  MEFV variant alleles were found in 24 (33.8%) of the gout patients and in 13 (26%) of the control subjects; the difference was not statistically significant. In the gout patients with a MEFV variant allele, the interval between the first two attacks was shorter (P = 0.014), and the platelet count was higher (P = 0.026), compared to the patients without a variant allele. In addition, the patients with a MEFV variant allele showed the higher incidence of tophus (8.5% vs. 1.4%) (P = 0.005) and the higher number of attacks per year (P = 0.001).
  
  
  CONCLUSIONS
  We propose that a variant allele of the MEFV gene may be responsible for the severity of gout.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Antalya Training and Research Hospital, Konyaaltı, Antalya, Turkey.
authors.forename: Ayse
authors.initials: A
authors.lastname: Balkarli
authors.affiliation: Department of Medical Biology, Pamukkale University Hospital, Kınıklı, Denizli, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Tepeli
authors.affiliation: Department of Orthopedics and Traumatology, Akdeniz University Hospital, Konyaaltı, Antalya, Turkey.
authors.forename: Huseyin
authors.initials: H
authors.lastname: Balkarli
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Pamukkale University Hospital, Kınıklı, Denizli, Turkey.
authors.forename: Arif
authors.initials: A
authors.lastname: Kaya
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Pamukkale University Hospital, Kınıklı, Denizli, Turkey.
authors.forename: Veli
authors.initials: V
authors.lastname: Cobankara
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006073:Gout / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011446:Prospective Studies; D000071198:Pyrin / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C000604192:MEFV protein, human; D000071198:Pyrin
keywords: MEFV gene variation; clinical course; familial Mediterranean fever; gout; pathogenesis