Abstract
BACKGROUND: Aggressive periodontitis (AgP) is associated with impaired polymorphonuclear leukocyte (PMN) chemotaxis toward bacterial N-formylpeptides. Formylpeptide receptors (FPRs) play a major role in guiding PMNs to infection sites. Previous work revealed a significant association between FPR1 single nucleotide polymorphism (SNP) 348T>C and AgP in African Americans. We tested the hypothesis that 348T impairs PMN chemotaxis by decreasing FPR mRNA expression, thereby increasing susceptibility to AgP. METHODS: Blood samples were obtained from African American subjects (37 AgP cases and 38 controls). Chemotaxis to N-formyl-methionine-leucine-phenylalanine by freshly isolated PMNs was assayed in a modified Boyden chamber. RNA was isolated from PMNs, and FPR1 gene expression was quantified by real-time polymerase chain reaction (PCR). To detect FPR1 5' SNPs, genomic DNA was isolated, and four fragments spanning the FPR1 5' region were PCR-amplified and sequenced. Haplotype associations between SNP 348T>C and 5' SNPs were analyzed. RESULTS: The homozygous 348T genotype was only found in AgP cases (P = 0.017; odds ratio, 18.9). Subjects with this genotype exhibited a significantly lower PMN chemotactic response relative to controls and to subjects with the 348C/C or 348T/C genotype (P <0.05). There were no significant differences in PMN FPR1 expression among subjects with the 348C/C, 348T/C, and 348T/T genotypes. Eleven FPR1 5' SNPs were detected, but none of the predicted haplotypes reflected associations with AgP or with 348T. CONCLUSIONS: Although the 348T/T genotype is relatively rare, it is associated with significantly impaired PMN chemotaxis and an increased risk for developing AgP in African Americans. These associations do not seem to be related to significant reductions in FPR1 transcripts in subjects expressing 348T.