Neutrophil Formylpeptide Receptor SNP 348C>T and Aggressive Periodontitis

Objectives: Neutrophil formylpeptide receptors (FPRs) play an important role in chemotaxis and bacterial recognition. We previously reported an association of the synonymous FPR single nucleotide polymorphism (SNP) 348C>T in African American Aggressive Periodontitis (AP) subjects. We assessed the relationship between FPR1 SNPs, neutrophil chemotaxis defects and susceptibility to AP;

Methods: Peripheral blood was drawn and genomic DNA isolated from 30 AP subjects and 33 controls. A polymorphic portion of the FPR1 coding region was amplified by PCR and sequenced to detect SNPs. HelixTreeŽ software was used for haplotype analyses of both groups. Neutrophils were isolated from 18 AP subjects and 28 controls by ficoll centrifugation and dextran sedimentation. Neutrophil chemotaxis was assayed for 30 min at 37° C in a modified Boyden chamber, using 10nM N-formyl-Met-Leu-Phe as the chemoattractant;

Results: Five previously identified SNPs (301G>C, 348C>T, 546C>A, 568A>T and 576T>C>G) were detected in the fragment analyzed. Frequency of SNP 348C>T was significantly higher (39%) in the AP group than controls (20%, P= 0.029). Seven cases, but none of the controls, were homozygous for 348T (P=0.004). Thirteen haplotypes with frequencies of at least 0.01 were identified in the case group, while eleven haplotypes were found in the control group. The magnitude of the neutrophil chemotactic response to formylpeptides was 19% lower in case subjects than in controls (P<0.001), whereas random migration was similar (P=1); Conclusion: Our findings suggest that African Americans with the 348T variant have an increased risk of developing AP and their neutrophils exhibit impaired chemotaxis to formylpeptides. Although the 348C>T polymorphism is synonymous, it maybe linked to other polymorphisms in the FPR promoter. This could lead to reduced FPR expression and impaired neutrophil chemotaxis. This phenomenon has been previously observed with the human a2 adrenergic receptor gene. Supported by NIH grant R21 DE017178.