title: Male sex coupled with articular manifestations cause a 4-fold increase in susceptibility to amyloidosis in patients with familial Mediterranean fever homozygous for the M694V-MEFV mutation.
abstract: OBJECTIVE
  Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever, serositis, and a predisposition to the development of amyloidosis. The wide clinical variability of the disease has been partly attributed to MEFV allelic heterogeneity and partly to the influence of additional genetic and/or environmental modifiers. Of these, male sex was found to influence disease penetrance and susceptibility to amyloidosis. We investigated the role of sex as an independent contributor to the phenotypic profile in FMF and further defined the factors affecting disease expression and severity.
  
  
  METHODS
  A total of 124 patients with FMF who were all homozygous for the M694V mutation, including 47 patients with nephropathic amyloidosis, were identified. A detailed chart review and physical examination were undertaken to determine demographic characteristics, history, clinical manifestations, and treatment, and we calculated the disease severity score from the Tel-Hashomer key.
  
  
  RESULTS
  A preponderance of male patients was documented (73:51; 1.4). The overall male:female ratio was significantly higher among patients with amyloidosis (32:15; 2.1) compared to patients without amyloidosis (41:36; 1.1). FMF severity scores, independently calculated for male and female patients, were equally high (9.5 +/- 3.0 and 9.7 +/- 2.8, respectively). The frequency of arthritic attacks, significantly higher in women than men (p = 0.015), remained notably higher in male FMF patients with amyloidosis compared to male FMF patients without amyloidosis (p = 0.002). Significant correlation between arthritis attacks and amyloidosis was found (R > 0.285, p < 0.001).
  
  
  CONCLUSIONS
  Susceptibility to renal amyloidosis is influenced both by sex and the occurrence of joint attacks, acting as 2 MEFV independent factors (OR 2.37, 95% CI 1.06-5.26 and OR 3.27, 95% CI 1.23-8.68, respectively).
authors.affiliation: Department of Human Genetics, Rambam Medical Center, Haifa, Israel. r.gerhoni@rambam.health.gov.il
authors.forename: Ruth
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: Riva
authors.initials: R
authors.lastname: Brik
authors.forename: Merav
authors.initials: M
authors.lastname: Lidar
authors.forename: Marwan
authors.initials: M
authors.lastname: Shinawi
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
mesh_terms: D000328:Adult; D000686:Amyloidosis / Q000453:epidemiology / Q000235:genetics*; D001168:Arthritis / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D003598:Cytoskeletal Proteins; D010505:Familial Mediterranean Fever / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006720:Homozygote; D006801:Humans; D008297:Male; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin; D012307:Risk Factors; D017678:Sex Distribution
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin