Host Susceptibility to Periodontitis

Host susceptibility to periodontal infection is controlled by genetic factors. As a step toward identifying and cloning these factors, we generated an A/J x BALB/cJ F2 mouse resource population. A genome-wide search for Quantitative Trait Loci (QTL) associated with periodontitis was performed. We aimed to quantify the phenotypic response of the progenies to periodontitis by microCT analysis, to perform a genome-wide search for QTL associated with periodontitis, and, finally, to suggest candidate genes for periodontitis. We were able to produce 408 F2 mice. All mice were co-infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria. Six weeks following infection, alveolar bone loss was quantified by computerized tomography (microCT) technology. We found normal distribution of the phenotype, with 2 highly significant QTL on chromosomes 5 and 3. A third significant QTL was found on chromosome 1. Candidate genes were suggested, such as Toll-like receptors (TLR) 1 and 6, chemokines, and bone-remodeling genes (enamelin, ameloblastin, and amelotin). This report shows that periodontitis in mice is a polygenic trait with highly significant mapped QTL.

[1]  W. Crielaard,et al.  Genetic susceptibility to periodontitis. , 2012, Periodontology 2000.

[2]  J. Reseland,et al.  Ameloblastin expression and putative autoregulation in mesenchymal cells suggest a role in early bone formation and repair. , 2011, Bone.

[3]  L. Shapira,et al.  Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis. , 2010, Periodontology 2000.

[4]  E. Weiss,et al.  Mouse model of experimental periodontitis induced by Porphyromonas gingivalis/Fusobacterium nucleatum infection: bone loss and host response. , 2009, Journal of clinical periodontology.

[5]  Nengjun Yi,et al.  Hierarchical Generalized Linear Models for Multiple Quantitative Trait Locus Mapping , 2009, Genetics.

[6]  Lior Shapira,et al.  Three-dimensional quantification of alveolar bone loss in Porphyromonas gingivalis-infected mice using micro-computed tomography. , 2005, Journal of periodontology.

[7]  A. Ritter,et al.  Periodontal Disease , 2005 .

[8]  Nengjun Yi,et al.  The Collaborative Cross, a community resource for the genetic analysis of complex traits , 2004, Nature Genetics.

[9]  F. Iraqi,et al.  Confirmation and dissection of QTL controlling resistanceto malaria in mice , 2004, Mammalian Genome.

[10]  T. Hart,et al.  Genes and gene polymorphisms associated with periodontal disease. , 2003, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[11]  F. Iraqi,et al.  Mapping of chromosomal regions influencing immunological responses to gastrointestinal nematode infections in mice , 2003, Parasite immunology.

[12]  F. Iraqi,et al.  Chromosomal regions controlling resistance to gastro-intestinal nematode infections in mice , 2003, Mammalian Genome.

[13]  D. Roopenian,et al.  Genetic susceptibility to chronic periodontal disease. , 2002, Microbes and infection.

[14]  A. Richmond,et al.  Developmental expression of two CXC chemokines, MIP-2 and KC, and their receptors. , 2001, Cytokine.

[15]  A. Greinacher,et al.  Polymorphisms of Fc gamma-receptors RIIa, RIIIa, and RIIIb in patients with adult periodontal diseases. , 2001, Genes and immunity.

[16]  A. Aderem,et al.  The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. C. Collins,et al.  A method for fine mapping quantitative trait loci in outbred animal stocks. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J C Gunsolley,et al.  Evidence of a substantial genetic basis for risk of adult periodontitis. , 2000, Journal of periodontology.

[19]  D. Roopenian,et al.  Genetic Control of Susceptibility toPorphyromonas gingivalis-Induced Alveolar Bone Loss in Mice , 2000, Infection and Immunity.

[20]  C. Haley,et al.  Fine mapping of trypanosomiasis resistance loci in murine advanced intercross lines , 2000, Mammalian Genome.

[21]  F. Iraqi FINE MAPPING OF QUANTITATIVE TRAIT LOCI USING ADVANCED INTERCROSS LINES OF MICE AND POSITIONAL CLONING OF THE CORRESPONDING GENES , 2000, Experimental lung research.

[22]  A. Korol,et al.  Single- and multiple-trait mapping analysis of linked quantitative trait loci. Some asymptotic analytical approximations. , 1999, Genetics.

[23]  J. D. Bartlett,et al.  Murine enamelin: cDNA and derived protein sequences. , 1998, Connective tissue research.

[24]  R. Page,et al.  Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. , 1997, Periodontology 2000.

[25]  G. Duff,et al.  The interleukin-1 genotype as a severity factor in adult periodontal disease. , 1997, Journal of clinical periodontology.

[26]  H. Herschman,et al.  Glucocorticoid-attenuated Response Genes Encode Intercellular Mediators, Including a New C-X-C Chemokine (*) , 1995, The Journal of Biological Chemistry.

[27]  M. Wilson Biological activities of lipopolysaccharides from oral bacteria and their relevance to the pathogenesis of chronic periodontitis. , 1995, Science progress.

[28]  D. Roopenian,et al.  Oral infection with Porphyromonas gingivalis and induced alveolar bone loss in immunocompetent and severe combined immunodeficient mice. , 1994, Archives of oral biology.

[29]  M. Soller,et al.  Selective DNA pooling for determination of linkage between a molecular marker and a quantitative trait locus. , 1994, Genetics.

[30]  B. Michalowicz Genetic risk factors for the periodontal diseases. , 1994, Compendium.

[31]  C. Cutler,et al.  A novel mouse model to study the virulence of and host response to Porphyromonas (Bacteroides) gingivalis , 1991, Infection and immunity.

[32]  P. Kolenbrander,et al.  Inhibition of coaggregation between Fusobacterium nucleatum and Porphyromonas (Bacteroides) gingivalis by lactose and related sugars , 1989, Infection and immunity.