Linkage disequilibrium analysis of case-control data: an application to generalized aggressive periodontitis

Several studies have shown a role for the involvement of interleukin (IL)-1 gene cluster polymorphisms in the risk of periodontal diseases. In the present study, we tested polymorphisms, derived from genes of the IL-1 cluster, for association with generalized aggressive periodontitis (GAP) through both allelic association and by constructing a linkage disequilibrium (LD) map of the 2q13?14 disease candidate region. The IL-1RN (VNTR) genotype distribution observed was significantly different in GAP and control subjects (P=0.019). We also observed some evidence for an association between GAP and the IL-1B+3953 polymorphism (P=0.039). The pattern of association in the region, represented as an LD map, identifies a recombination hot area between the IL-1B+3953 and IL-1B-511 polymorphisms. Multilocus modelling of association with disease gives a location for the peak association at the IL-1B+3953 marker, although support for the peak is not significant. Haplotype analysis identifies a IL-1B+3953?IL-1B-511 haplotype as having the lowest P-value in the region. Recognition of the presence of a recombination hot area between the IL-1B+3953 and IL-1B-511 polymorphisms will have an important bearing on future efforts to develop higher resolution SNP analysis in this region for both this and other diseases for which this cluster is implicated