title: Familial Mediterranean fever gene (MEFV) mutations and disease severity in systemic lupus erythematosus (SLE): implications for the role of the E148Q MEFV allele in inflammation.
abstract: OBJECTIVE
  Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients.
  
  
  METHODS
  The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis.
  
  
  RESULTS
  None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis (p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04-16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69-197.13).
  
  
  CONCLUSIONS
  Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature. In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.
authors.affiliation: Marmara University Faculty of Medicine, Istanbul, Turkey r.deniz@outlook.com.
authors.forename: R
authors.initials: R
authors.lastname: Deniz
authors.affiliation: Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Ozen
authors.affiliation: Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Yilmaz-Oner
authors.affiliation: Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Alibaz-Oner
authors.affiliation: Marmara University Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey.
authors.forename: C
authors.initials: C
authors.lastname: Erzik
authors.affiliation: Goztepe Training and Research Hospital, Department of Rheumatology, Istanbul, Turkey.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Aydin
authors.affiliation: Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey.
authors.forename: N
authors.initials: N
authors.lastname: Inanc
authors.affiliation: Marmara University Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Eren
authors.affiliation: Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Bayalan
authors.affiliation: Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Direskeneli
authors.affiliation: Marmara University Faculty of Medicine, Department of Rheumatology, Istanbul, Turkey.
authors.forename: P
authors.initials: P
authors.lastname: Atagunduz
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D000071198:Pyrin; D012720:Severity of Illness Index
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin
keywords: E148Q; MEFV; SLE; disease severity