Project 2: Genetic Epidemiology and Molecular Gene Mapping Studies of Early Onset Periodontitis Substantial evidence indicates that genetic differences among individuals influence risk of early onset periodontitis (EOP). However, this disease clearly has a complex etiology. Both heritable variation and factors in the environment (e.g., smoking, hygiene, exposure to pathogens) appear to interact in determining disease risk. Our previous studies demonstrated an association or interleukin-1 polymorphisms and EOP susceptibility. Other possible susceptibility genes were mapped to chromosomal regions but not yet specifically identified. We also initiated gene mapping studies of EOP-related phenotypes such as smoking behavior and serum immunoglobulins. Recent major advances in human molecular genomics and statistical genetic epidemiology provide greatly increased power in human molecular genomics and statistical genetic epidemiology provide greatly increased power to identify genes underlying complex traits such as EOP. We propose to apply these tools and approaches to follow up our previous findings for EOP by: i) verifying the role of IL-1 in EOP through analyses of additional IL-1 polymorphisms and additional EOP families and case-control subjects; ii) replicating our other gene mapping EOP findings using additional EOP families, identifying disease genes via mutational screening, evaluating new candidate gene polymorphisms and, when assay technologies mature, performing genome-wide disequilibrium mapping; iii) analyzing risk factor phenotypes such as smoking and immunoglobulin levels, both as covariates for EOP analyses and as highly heritable traits of direct interest; and iv) developing and evaluating quantitative measurements of EOP in lieu of the current discrete disease state classification and using these quantitative traits for re-analyses of our gen mapping data with variance components analyses and other quantitative trait locus (QTL) methods.
| Griffiths, Rachel; Barbour, Suzanne (2010) Lipoproteins and lipoprotein metabolism in periodontal disease. Clin Lipidol 5:397-411 |
