Author(s):
Zhang, Y ; Syed, R ; Uygar, C ; Pallos, Débora ; Gorry, MC ; Firatli, E ; Cortelli, José Roberto ; VanDyke, TE ; Hart, Patricia Suzanne ; Feingold, E ; Hart, Thomas Charles
Date: 2019
Origin: Oasisbr
Subject(s): Fpr1; Polymorphism; Aggressive Periodontitis; Ethnic; Neutrophil; Formyl Peptide Receptor; Localized Juvenile Periodontitis; Early-Onset Periodontitis; Cdna; Identification; Neutrophils; Chemotaxis; Adhesion; Binding; Genetics & Heredity; Immunology; Genetics & Heredity; Immunology
Description
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National Institute of Dental and Craniofacial Research (NIDCR)
Polymorphonuclear neutrophils (PMNs) are attracted to sites of infection by N-formylpeptide (fMLP) chemoattractants. The high-affinity fMLP receptor (FPR1) of phagocytic cells interacts with bacterial fMLP and mediates chemotaxis, degranulation, and superoxide production. These cellular functions are disrupted in PMN from aggressive periodontitis (AP) patients. Two FPR1 gene single nucteotide polymorphisms (SNPs), c.329T> C and c.378C> G, have been associated with a localized form of AP in African-American patients. To evaluate the generality of these SNPs in AP patients, we sequenced a 363 bp interval of the FPR1 gene in an ethnically diverse group of patients (n = 111) and controls (n = 115). Neither c.329T> C nor c.378C> G were detected in the 452 alleles sequenced. Six SNPs were identified including two located in the FPR1 second extracellular loop that were significantly associated with the AP phenotype in African-American patients (p.R190W, P = 0.0033; and p.N192K, P = 0.0018). These two SNPs show three predominant haplotypes, each associated with a different disease risk in African-Americans. These data do not support the hypothesis that the FPR1 SNPs c.329T> C and c.378C> G play an etiologic role in aggressive periodontitis, but do suggest that SNPs in the second extracellular loop may be etiologically important.
Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Pittsburgh, PA 15261 USA; Universidade de Taubaté (Unitau), Sch Dent, Dept Periodont; Univ Istanbul, Sch Dent, Dept Periodontol, Istanbul, Turkey; Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA; Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA
