title: Functional polymorphisms of the FPR1 gene and aggressive periodontitis in Japanese.
abstract: Aggressive periodontitis (AgP), a severe and early onset type of periodontitis, is thought to be subject to significant genetic background effects. Formyl peptide receptor 1 (FPR1) is a gene strongly implicated in AgP. To determine whether variations in this gene are associated with AgP, we performed an association study with 49 AgP patients and 373 controls using 30 variations identified by sequencing the 21.1-kb gene region. Five polymorphisms (-12915C>T, -10056T>C, -8430A>G, 301G>C, and 546C>A) showed significant association with AgP. Polymorphonuclear neutrophils from subjects carrying the -12915T allele expressed significantly lower levels of FPR1 transcripts than those homozygous for the -12915C allele. Furthermore, the -12915T allele decreased activity of transcriptional regulation in a luciferase assay. Haplotype association analysis with three SNPs (-12915C>T, 301G>C, and 546C>A) revealed that one haplotype (-12915T-301G-546C) was significantly represented in AgP patients (p=0.000020). Thus, altered FPR1 function might confer increased risk to AgP.
authors.affiliation: Periodontology, Department of Hard Tissue Engineering, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Gunji
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Onouchi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Sayaka
authors.initials: S
authors.lastname: Katagiri
authors.forename: Hisashi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Arakawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Noguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
authors.forename: Isao
authors.initials: I
authors.lastname: Ishikawa
mesh_terms: D000328:Adult; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D010518:Periodontitis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044042:Receptors, Formyl Peptide / Q000235:genetics*
chemical_list: C469986:FPR1 protein, human; D044042:Receptors, Formyl Peptide