Single Nucleotide Polymorphisms of the N‐Formyl Peptide Receptor in Localized Juvenile Periodontitis

Gwinn, Maureen R.; Sharma, Ashu; Nardin, Ernesto De

doi:10.1902/jop.1999.70.10.1194

Cited by 77 publications

(72 citation statements)

References 35 publications

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“…Five of the eight SNPs identified within exon 2 (nucleotide #301, 348, 546, 568, and 576) of the FPR1 gene are located in the genetic interval sequenced for this study. The two SNPs at nucleotides 329 and 378, previously reported to be associated with a localized form of AP by Gwinn et al, 12 were not detected in any of the 111 AP patients (222 chromosomes) nor in any of the 115 controls (230 chromosomes). We did not detect any variation in these two nucleotide locations among any of the 226 individuals tested.…”

Section: Resultsmentioning

confidence: 67%

“…The analysis identified a total of six SNPs in this genetic interval. We did not identify a single case of the disease-associated SNPs reported by Gwinn et al 12 in any of the 452 chromosomes sequenced. Of the SNPs identified, three are non-synonymous and three are synonymous, including one novel SNP.…”

Section: Introductionmentioning

confidence: 70%

“…Two missense mutations, p.F110S and p.C126W, were reported in the homozygous state in 29 of 30 patients, but were not found in any other individuals including healthy controls and individuals with adult, chronic forms of periodontitis. 12 While the disease association with these SNPs appears compelling, the homozygous presence of these SNPs in AP patients is not consistent with the autosomal dominant mode of transmission reported for AP. 19 Although these findings are not consistent with these SNPs being the loci of major effect for AP, they could represent modifying loci.…”

Section: Discussionmentioning

confidence: 90%

“…10,11 Alterations of two codons, one in the second transmembrane domain (c.329T4C/p.F110S) and one in the second intracellular loop (c.378C4G/p.C126W) of the fMLP receptor, have been reported to be significantly associated with a localized form of AP in African American patients. 12 Gwinn et al 12 reported that the mutant variant of either one or both single nucleotide polymorphisms (SNPs) (c.329T4C and c.378C4G) are present in 29 of 30 African-American patients with a localized form of AP previously called localized juvenile periodontitis. 13 Neither of these disease-associated SNPs was found in any other periodontitis or control groups, suggesting a remarkable disease association.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients

et al. 2003

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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.329T4C and c.378C4G, 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 ¼ 111) and controls (n ¼ 115). Neither c.329T4C nor c.378C4G 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 ¼ 0.0033; and p.N192K, P ¼ 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.329T4C and c.378C4G play an etiologic role in aggressive periodontitis, but do suggest that SNPs in the second extracellular loop may be etiologically important.

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Section: Resultsmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients

et al. 2003

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“…In a previous association study of FPR2 genetic variants, two SNPs (F110S and C126W), located in the open reading frame of FPR2, were found to be associated with juvenile periodontitis. 24 These SNPs were not analyzed in our study, because the design of this study was based on the NCBI DB and these two SNPs were not in NCBI DB. These SNPs were not analyzed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and Aspirin exacerbated respiratory diseases

et al. 2012

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Aspirin-exacerbated respiratory diseases (AERD) are associated with the metabolism of arachidonic acid. FPR2 (formyl peptide receptor2) is a high-affinity ligand receptor for potent anti-inflammatory lipid metabolites: lipoxins. Thus, functional alterations of the FPR2 may contribute to AERD. We investigated the relationship between single-nucleotide polymorphisms (SNPs) in the FPR2 and AERD. Asthmatics were categorized into AERD o15% decreases in forced expiratory volume in one second (FEV 1 ), and/or naso-ocular reactions after oral aspirin challenge (n¼170) and aspirin-tolerant asthma (ATA, n¼268). In all, 11 SNPs were genotyped. FPR2 protein expressions on CD14-positive monocytes in peripheral blood were measured using flow cytometric analysis. We performed RT-PCR of the FPR2 mRNA expressed by peripheral blood mononuclear cells. Logistic regression analysis showed that the minor allele frequency of FPR2 À4209T4G (rs1769490) in intron 2 was significantly lower in the AERD group (n¼170) than in the ATA group (n¼268) (P¼0.006, P corr ¼0.04, recessive model). The decline of FEV 1 after aspirin challenge was significantly lower in the subjects with GG homozygotes of FPR2 À4209T4G than those with the other genotypes (P¼0.0002). Asthmatic homozygotes for FPR2 À4209T4G minor allele exhibited significantly higher FPR2 protein expression in CD14-positive monocytes than did those with the common allele of FPR2 À4209T4G allele (P¼0.01). There was no difference in the expression of the wild form and the exon 2 deleted variant form of FPR2 gene according to the genotypes of FPR2 À4209T4G. The minor allele at FPR2 À4209T4G may have a protective role against the development of AERD, via increase of FPR2 protein expression in inflammatory cells.

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The immediate protective response to microbial challenge

González‐Navajas

Corr

2014

Eur J Immunol

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The innate immune system detects infection and tissue injury through different families of pattern-recognition receptors (PRRs), such as Toll-like receptors. Most PRR-mediated responses initiate elaborate processes of signaling, transcription, translation, and secretion of effector mediators, which together require time to achieve. Therefore, PRRmediated processes are not active in the early phases of infection. These considerations raise the question of how the host limits microbial replication and invasion during this critical period. Here, we examine the crucial defense mechanisms, such as antimicrobial peptides or extracellular traps, typically activated within minutes of the initial infection phase, which we term the "immediate protective response". Deficiencies in different components of the immediate protective response are often associated with severe and recurrent infectious diseases in humans, highlighting their physiologic importance. Keywords: Antimicrobial response r Infection r Innate immunity IntroductionInfection activates the innate immune response through different families of germline-encoded pattern-recognition receptors (PRRs), among which the Toll-like receptors (TLRs) are the most studied. These PRRs are expressed on the cell membranes or in the cytosol of immune and other cells and respond to microbial signature compounds, known as pathogen-associated molecular patterns (PAMPs). As a result, an acute inflammatory/defense response is initiated that is able to target a wide range of microbial agents and/or infected cells.Interestingly, tissue injury caused by sterile insults, such as trauma or hypoxia, activates a similar early inflammatory response. One potential evolutionary explanation for these similarities is that tissue injury usually results in the disruption of physiological barriers followed by microbial invasion. Another possibility is that microbes can also cause cell necrosis, so responding to tissue injury may be an indirect way of detecting microbial invasion. Thus, the mammalian host has developed a system Correspondence: Dr. José M. González-Navajas e-mail: gonzalez_josnav@gva.es of endogenous warning signals that are constitutively available and are rapidly activated in the very early phase of both sterile and nonsterile inflammation. These warning signals are provoked by alarmins or danger-associated molecular patterns. Alarmins are multifunctional endogenous molecules of structural heterogeneity, such as ATP, high-mobility group protein B1, or heat shock proteins, that are passively released following nonapoptotic cell death or actively secreted by leukocytes and epithelial cells [1]. As potent inducers of inflammatory responses, alarmins contribute to the defense against pathogens and promote tissue repair, but excessive alarmin secretion is also associated with acute and chronic inflammatory conditions [2].Stimulation of immune cells by endogenous alarmins or microbial derived PAMPs evokes similar signaling cascades and activates similar transcription factors [3] that c...

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Single Nucleotide Polymorphisms of the N‐Formyl Peptide Receptor in Localized Juvenile Periodontitis

Abstract: This study suggests that a molecular alteration in the second intracellular loop of the FMLP receptor molecules in LP patients may play a role in the decreased chemotactic activity reported for some LJP patients.

Cited by 77 publications

References 35 publications

Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients

Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients

Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and Aspirin exacerbated respiratory diseases

The immediate protective response to microbial challenge

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