title: The contribution of SAA1 polymorphisms to Familial Mediterranean fever susceptibility in the Japanese population.
abstract: OBJECTIVE
  Familial Mediterranean Fever (FMF) has traditionally been considered to be an autosomal-recessive disease, however, it has been observed that substantial numbers of patients with FMF possess only 1 demonstrable MEFV mutation. The clinical profile of familial Mediterranean fever (FMF) may be influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors.
  
  
  RESULTS
  In view of the inflammatory nature of FMF, we investigated whether serum amyloid A (SAA) and interleukin-1 beta (IL-1β) gene polymorphisms may affect the susceptibility of Japanese patients with FMF. The genotypes of the -13C/T SNP in the 5'-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 83 Japanese patients with FMF and 200 healthy controls. The same samples were genotyped for IL-1β-511 (C/T) and IL-1 receptor antagonist (IL-1Ra) variable number of tandem repeat (VNTR) polymorphisms. There were no significant differences between FMF patients and healthy subjects in the genotypic distribution of IL-1β -511 (C/T), IL-1Ra VNTR and SAA2 polymorphisms. The frequencies of SAA1.1 allele were significantly lower (21.7% versus 34.0%), and inversely the frequencies of SAA1.3 allele were higher (48.8% versus 37.5%) in FMF patients compared with healthy subjects. The frequency of -13T alleles, associated with the SAA1.3 allele in the Japanese population, was significantly higher (56.0% versus 41.0%, p=0.001) in FMF patients compared with healthy subjects.
  
  
  CONCLUSIONS
  Our data indicate that SAA1 gene polymorphisms, consisting of -13T/C SNP in the 5'-flanking region and SNPs within exon 3 (2995C/T and 3010C/T polymorphisms) of SAA1 gene, are associated with susceptibility to FMF in the Japanese population.
authors: Clinical Research Center, Department of General Internal Medicine and NHO Nagasaki Medical Center, Kubara, Omura, Japan. migita@nmc.hosp.go.jp
authors: Kiyoshi
authors: K
authors: Migita
authors: Kazunaga
authors: K
authors: Agematsu
authors: Junya
authors: J
authors: Masumoto
authors: Hiroaki
authors: H
authors: Ida
authors: Seiyo
authors: S
authors: Honda
authors: Yuka
authors: Y
authors: Jiuchi
authors: Yasumori
authors: Y
authors: Izumi
authors: Yumi
authors: Y
authors: Maeda
authors: Ritei
authors: R
authors: Uehara
authors: Yoshikazu
authors: Y
authors: Nakamura
authors: Tomohiro
authors: T
authors: Koga
authors: Atsushi
authors: A
authors: Kawakami
authors: Munetoshi
authors: M
authors: Nakashima
authors: Yuichiro
authors: Y
authors: Fujieda
authors: Fumiaki
authors: F
authors: Nonaka
authors: Katsumi
authors: K
authors: Eguchi
authors: Hiroshi
authors: H
authors: Furukawa
authors: Tadashi
authors: T
authors: Nakamura
authors: Minoru
authors: M
authors: Nakamura
authors: Michio
authors: M
authors: Yasunami
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D007564:Japan; D008297:Male; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000685:Serum Amyloid A Protein / Q000235:genetics*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; C521404:SAA1 protein, human; D000685:Serum Amyloid A Protein