Analysis of genetic polymorphisms as risk factors for Aggressive Periodontitis

This PhD consisted of a series of studies aiming at detecting genetic risk factors for Aggressive Periodontitis (AgP). AgP is a destructive disease of the periodontium affecting around 1% of the population and leading to early tooth loss. Microbiological and environmental factors are thought to act on a genetically susceptible host to determine AgP. We conducted a casecontrol association study on 224 AgP patients (both Generalised AgP and Localised AgP) and 231 healthy controls to detect differences in genotype distributions of 13 single nucleotide polymorphisms (SNPs). The selected SNPs included FcR and FPR, NADPH oxidase, IL-6, TNF-a and VDR polymorphisms. Further studies on subsets of patients were conducted to detect associations between these SNPs and classical features of AgP: disease severity, familial aggregation, presence of periodontopathogenic bacteria and neutrophil hyperactivity. The NADPH p22phox 242 polymorphism was associated with the AgP trait and with disease severity. The IL-6 -174 SNP was associated with LAgP and with increased detection o f periodontopathogenic bacteria. The FcyRIIIb NA polymorphism was associated with GAgP, while FcyR haplotypes were linked with AgP in Blacks and FcyRIIa was associated with familial aggregation of the AgP phenotype. The VDR Taq-I polymorphism showed a trend for association with AgP in smokers. The overall results of the study provide two possible pathogenic pathways leading to AgP: one is mediated through an excessive inflammatory response triggered by the presence of specific bacteria in individuals with hyper-responsive genotypes (NADPH p22phox 242 T allele, FcyRIIIb NA1 homozygosity, IL-6 -174 G homozygosity); the second is initiated by an increased susceptibility to bacterial colonization (FcyRIIa R