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

• Published in: Genes and immunity Vol. 6; no. 1; pp. 44 - 52
• Main Authors: Scapoli, C, Trombelli, L, Mamolini, E, Collins, A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.02.2005
• Subjects: Analysis; Case-Control Studies; Chromosome Mapping; Cytokines; Gene expression; Gene polymorphism; Genes; Genetic aspects; Genetic Predisposition to Disease; Gum disease; Haplotypes; Health aspects; Humans; IL-1β; Interleukin 1; Interleukin 1 receptors; Interleukin-1 - genetics; Linkage (Genetics); Linkage analysis; Linkage disequilibrium; Linkage Disequilibrium - genetics; Multigene Family - genetics; Periodontal diseases; Periodontitis; Periodontitis - genetics; Polymorphism, Single Nucleotide - genetics; Power; Recombination; Single-nucleotide polymorphism; Italy
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6364152

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.