ABSTRACT
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 nucleotide 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.
Subject(s)
Aggressive Periodontitis/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Immunologic/genetics , Receptors, Peptide/genetics , Black or African American/statistics & numerical data , Amino Acid Sequence , Base Sequence , Chi-Square Distribution , Gene Frequency/genetics , Humans , Molecular Sequence Data , Receptors, Formyl Peptide , Receptors, Immunologic/chemistry , Receptors, Peptide/chemistryABSTRACT
Freeze-dried bone allograft (FDBA) which either had or had not been sterilized by exposure to ethylene oxide (EtO) prior to lyophilization was obtained from two commercial sources. EtO-sterilized FDBA was reexposed to EtO as a positive control. Gas chromatograph assays revealed that three out of four commercially obtained EtO sterilized FDBA had no detectable EtO, with one sample having 0.21 parts per million (PPM). Surprisingly, 0.24 PPM was detected in one sample which had not been sterilized with EtO gas. This was presumed due to contamination from a gas-sterilized rubber stopper. In the cell toxicity study, FDBA and human gingival fibroblasts (HGF) were added simultaneously, incubated for 72 h, and fixed and stained. Samples of FDBA sterilized with EtO which were free of EtO did not alter HGF growth. However, the positive control FDBA which contained 0.72 PPM EtO had a deleterious effect on HGF. FDBA with EtO residuals caused morphologic change in HGF.
