The Contribution of SAA1 Polymorphisms to Familial Mediterranean Fever Susceptibility in the Japanese Population

• Published in: PloS one Vol. 8; no. 2; p. e55227
• Main Authors: Migita, Kiyoshi, Agematsu, Kazunaga, Masumoto, Junya, Ida, Hiroaki, Honda, Seiyo, Jiuchi, Yuka, Izumi, Yasumori, Maeda, Yumi, Uehara, Ritei, Nakamura, Yoshikazu, Koga, Tomohiro, Kawakami, Atsushi, Nakashima, Munetoshi, Fujieda, Yuichiro, Nonaka, Fumiaki, Eguchi, Katsumi, Furukawa, Hiroshi, Nakamura, Tadashi, Nakamura, Minoru, Yasunami, Michio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.02.2013; Public Library of Science (PLoS)
• Subjects: Adult; Alleles; Amyloid; Asian Continental Ancestry Group - genetics; Biology; Case-Control Studies; Demography; Disease; Disease susceptibility; Environmental factors; Familial Mediterranean fever; Familial Mediterranean Fever - genetics; Family medical history; Female; Fever; Gene frequency; Gene Frequency - genetics; Genes; Genetic aspects; Genetic Loci - genetics; Genetic Predisposition to Disease; Genotypes; Heterogeneity; Hospitals; Humans; Inflammation; Interleukin; Interleukin 1; Interleukin 1 receptor antagonist; Interleukin 1 Receptor Antagonist Protein - genetics; Interleukin-1beta - genetics; Interleukins; Internal medicine; Japan; Male; Medicine; Mutation; Mutation - genetics; Patients; Periodic disease; Polymorphism, Single Nucleotide - genetics; Population; Population genetics; Proteins; Public health; Pyrin protein; Rheumatoid arthritis; Rheumatology; Serum Amyloid A Protein - genetics; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Tumor necrosis factor-TNF; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055227

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. 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. 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.