title: Linkage disequilibrium analysis of case-control data: an application to generalized aggressive periodontitis.
abstract: 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.
authors.affiliation: Department of Biology, University of Ferrara, I-44100 Ferrara, Italy. scc@unife.it
authors.forename: C
authors.initials: C
authors.lastname: Scapoli
authors.forename: L
authors.initials: L
authors.lastname: Trombelli
authors.forename: E
authors.initials: E
authors.lastname: Mamolini
authors.forename: A
authors.initials: A
authors.lastname: Collins
mesh_terms: D016022:Case-Control Studies; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics*; D010518:Periodontitis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D007375:Interleukin-1