Linkage disequilibrium of interleukin-1 genetic polymorphisms with early-onset periodontitis

Scott R. Diehl, Yue Fen Wang, Carol N. Brooks, John A. Burmeister, Joseph V. Califano, Shengbiao Wang, Harvey A. Schenkein

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126 Scopus citations


Background: Genetic polymorphisms at interleukin (IL)-1α and IL-1ß were recently suggested to be associated with severity of adult periodontitis. We evaluated whether these polymorphisms might also be associated with early-onset periodontitis (EOP) in 28 African American families and 7 Caucasian American families with 2 or more affected members. Methods: Genomic DNA from peripheral blood was amplified, followed by restriction endonuclease digestion and acrylamide gel electrophoresis to distinguish alleles of different fragment sizes. Genetic epidemiological methods suitable for family data were used that are robust to false-positive findings due to mismatching of cases and controls or mixed subpopulations of different ethnic or geographic origin. The 2 major EOP subtypes, localized juvenile periodontitis (LJP), and generalized early-onset periodontitis (G-EOP, encompassing rapidly progressive periodontitis and generalized juvenile periodontitis), were analyzed both separately and together. Results: We obtained highly significant evidence of linkage disequilibrium for both African American and Caucasian G-EOP subjects. A similar trend was noted for LJP. The IL-1 alleles associated with high risk of EOP had been suggested previously to be correlated with low risk for severe adult periodontitis. Disequilibrium with G-EOP was equally strong for smoking and non-smoking subjects. IL-1α and IL-1ß polymorphisms were in strong disequilibrium with each other in Caucasians, but not in African Americans. Haplotype analyses evaluating both polymorphisms simultaneously indicated that the IL-1ß variant is likely to be most important for EOP risk. Sibpair linkage analyses, by contrast, provided only marginal support for a gene of very major effect on EOP risk attributable to these IL-1 polymorphisms. Conclusions: Recent theoretical analyses indicate that our findings are most consistent with an interpretation of EOP as a complex, oligogenic disorder, with IL-1 genetic variation contributing an important but not exclusive influence on disease risk.

Original languageEnglish (US)
Pages (from-to)418-430
Number of pages13
JournalJournal of periodontology
Issue number4
StatePublished - Apr 1999
Externally publishedYes


  • Interleukin-1
  • Periodontitis, early-onset/etiology
  • Periodontitis, juvenile/etiology
  • Polymorphism
  • Racial stocks

ASJC Scopus subject areas

  • Periodontics


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