PLoS ONE (Jan 2013)

The contribution of SAA1 polymorphisms to Familial Mediterranean fever susceptibility in the Japanese population.

  • Kiyoshi Migita,
  • Kazunaga Agematsu,
  • Junya Masumoto,
  • Hiroaki Ida,
  • Seiyo Honda,
  • Yuka Jiuchi,
  • Yasumori Izumi,
  • Yumi Maeda,
  • Ritei Uehara,
  • Yoshikazu Nakamura,
  • Tomohiro Koga,
  • Atsushi Kawakami,
  • Munetoshi Nakashima,
  • Yuichiro Fujieda,
  • Fumiaki Nonaka,
  • Katsumi Eguchi,
  • Hiroshi Furukawa,
  • Tadashi Nakamura,
  • Minoru Nakamura,
  • Michio Yasunami

DOI
https://doi.org/10.1371/journal.pone.0055227
Journal volume & issue
Vol. 8, no. 2
p. e55227

Abstract

Read online

Background/aimsFamilial 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.Methodology/principal findingsIn 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/significanceOur 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.