title: Genetic risk factors of amyloidogenesis in familial Mediterranean fever.
abstract: OBJECTIVE
  Evaluation of the risk factors, and phenotype-genotype correlation of familial Mediterranean fever (FMF) gene (MEFV) and serum amyloid A1 (SAA1) gene polymorphisms in renal amyloidosis.
  
  
  METHODS
  We investigated MEFV and SAA1 genotypes (alpha, beta, and gamma isoforms) in 50 FMF patients and 50 healthy children. Tel-Hashomer criteria were used for the diagnosis and severity scoring of FMF.
  
  
  RESULTS
  The most common MEFV mutation and SAA1 genotype were M694V/M694V (n = 26/50) and SAA1 alpha/alpha (n = 26/50), respectively. Positive family history for amyloidosis was significantly higher (p < 0.001) with more severe clinical course (p = 0.006) in the amyloidosis group than the non-amyloid group. In M694V/M694V mutation, erysipelas-like skin erythema (p = 0.029), arthritis (p = 0.004), arthralgia (p < 0.001) were significantly more frequent with higher severity scores (p = 0.008) than the patients with other mutations. Comparison of the SAA1 alpha/alpha genotype with other genotypes revealed more frequent arthritis (p = 0.003) in the SAA1 alpha/alpha genotype. In amyloidosis group patients having both M694V/M694V and SAA1 alpha/alpha genotypes were the largest subgroup (n = 14, p < 0.001). Logistic regression analysis for amyloidosis corrected risk revealed a 1.2 times increase in M694V/M694V, a 2.4 times increase in SAA1 alpha/alpha genotypes and a 2.5 times increase when both are together.
  
  
  CONCLUSIONS
  Positive family history for amyloidosis and presence of SAA1 alpha/alpha genotype in M694V/M694V mutation may predispose to amyloidosis by increasing the clinical severity. Therefore, in such children early colchicine treatment might be recommended even if they are asymptomatic.
authors.affiliation: Mersin University Faculty of Medicine, Department of Pediatric Nephrology, Mersin, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Delibaş
authors.forename: Ayşe
authors.initials: A
authors.lastname: Oner
authors.forename: Banu
authors.initials: B
authors.lastname: Balci
authors.forename: Gulay
authors.initials: G
authors.lastname: Demircin
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bulbul
authors.forename: Kenan
authors.initials: K
authors.lastname: Bek
authors.forename: Ozlem
authors.initials: O
authors.lastname: Erdoğan
authors.forename: Sahika
authors.initials: S
authors.lastname: Baysun
authors.forename: Engin
authors.initials: E
authors.lastname: Yilmaz
mesh_terms: D000293:Adolescent; D000328:Adult; D000686:Amyloidosis / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008499:Medical Records; D008715:Methionine; D000685:Serum Amyloid A Protein / Q000235:genetics; D012720:Severity of Illness Index; D014633:Valine
chemical_list: D000685:Serum Amyloid A Protein; D008715:Methionine; D014633:Valine