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Functional polymorphisms of the FPR1 gene and aggressive periodontitis in Japanese.

Gunji T, Onouchi Y, Nagasawa T, Katagiri S, Watanabe H, Kobayashi H, Arakawa S, Noguchi K, Hata A, Izumi Y, Ishikawa I

Periodontology, Department of Hard Tissue Engineering, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.

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.

Published 26 October 2007 in Biochem Biophys Res Commun, 364(1): 7-13.
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