title: Prevalence and significance of the familial Mediterranean fever gene mutation encoding pyrin Q148.
abstract: Familial Mediterranean fever (FMF) is caused by more than 25 mutations in the gene MEFV, which encodes pyrin (marenostrin), a protein implicated in the regulation of neutrophil activity. Pyrin Q148, is one of the five most common variants in populations in which FMF typically occurs. Our identification of the pyrin Q148 allele in several patients from ethnic groups in which FMF is not classically recognized who had longstanding fevers or AA amyloidosis prompted us to study the prevalence of pyrin Q148 in healthy British, Indian and Chinese subjects. The gene frequency was also sought in 50 British Caucasian patients with inflammatory arthritis, 25 of whom had AA amyloidosis, five Punjabi Indians with AA amyloidosis complicating inflammatory arthritis, and seven British Caucasian patients with uncharacterized longstanding fever syndromes. The allele frequency for pyrin Q148 was 21%, 15% and 0%, respectively, among Punjabi Indian, Chinese and Caucasian British controls, and was significantly increased among the patients with AA amyloidosis and the patients with obscure fever syndromes (p<0.01). Pyrin Q148 is a polymorphism and occurs widely in global terms, and, although it may cause FMF when associated with certain other MEFV mutations, homozygosity for Q148 alone must usually be insufficient to produce FMF in the populations studied. The association of pyrin Q148 with AA amyloidosis and with obscure chronic inflammatory diseases suggests the variant may augment inflammation non-specifically, which might have been beneficial during evolution, but could potentially exacerbate many chronic inflammatory disorders.
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, London, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Booth
authors.forename: H J
authors.initials: HJ
authors.lastname: Lachmann
authors.forename: J D
authors.initials: JD
authors.lastname: Gillmore
authors.forename: S E
authors.initials: SE
authors.lastname: Booth
authors.forename: P N
authors.initials: PN
authors.lastname: Hawkins
mesh_terms: D000328:Adult; D017668:Age of Onset; D002648:Child; D003598:Cytoskeletal Proteins; D010505:Familial Mediterranean Fever / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008131:London / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin