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Variants in the interleukin-1 alpha and beta genes, and the risk for periodontal disease in dogs

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Abstract

Elevated levels of interleukin-1 (IL-1) have been shown to amplify the inflammatory response against periodontopathogenic bacteria. In humans, polymorphisms in the IL1A and IL1B genes are the most well-studied genetic polymorphisms associated with periodontal disease (PD). In contrast to human, there is a lack of knowledge on the genetic basis of canine PD. A case–control study was conducted in which a molecular analysis of dog IL1A and IL1B genes was performed. Of the eight genetic variants identified, seven in IL1A gene and one in IL1B gene, IL1A/1_g.388A >C and IL1A/1_g.521T >A showed statistically significant differences between groups (adjusted OR (95% CI): 0.15 (0.03–0.76), P= 0.022; 5.76 (1.03–32.1), P= 0.046, respectively). It suggests that in the studied population the IL1A/1_g.388C allele is associated with a decreased PD risk, whereas the IL1A/1_g.521A allele can confer an increased risk. Additionally, the IL1A/2_g.515G >T variation resulted in a change of amino acid, i.e. glycine to valine. In silico analysis suggests that this change can alter protein structure and function, predicting it to be deleterious or damaging. This work suggests that IL1 genetic variants may be important in PD susceptibility in canines.

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References

  • Adzhubei I. A., Schmidt S., Peshkin L., Ramensky V. E., Gerasimova A., Bork P. et al. 2010 A method and server for predicting damaging missense mutations. Nat. Methods 7, 248–249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albuquerque C., Morinha F., Requicha J., Dias I., Guedes-Pinto H., Viegas C. et al. 2014 A case–control study between interleukin-10 gene variants and periodontal disease in dogs. Gene 539, 75–81.

    Article  CAS  PubMed  Google Scholar 

  • Albuquerque C., Morinha F., Requicha J., Martins T., Dias I., Guedes-Pinto H. et al. 2012 Canine periodontitis: the dog as an important model for periodontal studies. Vet. J. 191, 299–305.

    Article  PubMed  Google Scholar 

  • Amano A. 2010 Host–parasite interactions in periodontitis: microbial pathogenicity and innate immunity. Periodontol. 2000 54, 9–14.

    Article  Google Scholar 

  • Arnold K., Bordoli L., Kopp J. and Schwede T. 2006 The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22, 195–201.

    Article  CAS  PubMed  Google Scholar 

  • Berger P., McConnell J. P., Nunn M., Kornman K. S., Sorrell J., Stephenson K. et al. 2002 C-reactive protein levels are influenced by common IL-1 gene variations. Cytokine 17, 171–174.

    Article  CAS  PubMed  Google Scholar 

  • Bioque G., Crusius J. B. A., Koutroubakis I., Bouma G., Kostense P. J., Meuwissen S. G. M. et al. 1995 Allelic polymorphism in IL-1 β and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease. Clin. Exp. Immunol. 102, 379–383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown B. D., Nsengimana J., Barrett J. H., Lawrence R. A., Steiner L., Cheng S. et al. 2010 An evaluation of inflammatory gene polymorphisms in sibships discordant for premature coronary artery disease: the GRACE-IMMUNE study. BMC Med. 8, 5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Carter S. D., Barnes A. and Gilmore W. H. 1999 Canine rheumatoid arthritis and inflammatory cytokines. Vet. Immunol. Immunopathol. 69, 201–214.

    Article  CAS  PubMed  Google Scholar 

  • Casini-Raggi V., Kam L., Chong Y. J., Fiocchi C., Pizarro T. T. and Cominelli F. 1995 Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease: a novel mechanism of chronic intestinal inflammation. J. Immunol. 154, 2434–2440.

    CAS  PubMed  Google Scholar 

  • Choi Y., Sims G. E., Murphy S., Miller J. R. and Chan A. P. 2012 Predicting the functional effect of amino acid substitutions and indels. PLoS One 7, e46688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clements D. N., Short A. D., Barnes A., Kennedy L. J., Ferguson J. F., Butterworth S. J. et al. 2010 A candidate gene study of canine joint diseases. J. Hered. 101, 54–60.

    Article  CAS  PubMed  Google Scholar 

  • Cooper D. N. 2010 Functional intronic polymorphisms: buried treasure awaiting discovery within our genes. Hum. Genomics 4, 284–288.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cullinan M. P. and Seymour G. J. 2013 Periodontal disease and systemic illness: will the evidence ever be enough? Periodontol. 2000 62, 271–286.

    Article  PubMed  Google Scholar 

  • Cullinan M. P., Westerman B., Hamlet S. M., Palmer J. E., Faddy M. J., Lang N. P. et al. 2001 A longitudinal study of interleukin-1 gene polymorphisms and periodontal disease in a general adult population. J. Clin. Periodontol. 28, 1137–1144.

    Article  CAS  PubMed  Google Scholar 

  • Curtis D., Knight J. and Sham P. C. 2006 Program report: GENECOUNTING support programs. Ann. Hum. Genet. 70, 277–279.

    Article  CAS  PubMed  Google Scholar 

  • Delima A. J., Karatzas S., Amar S. and Graves D. T. 2002 Inflammation and tissue loss caused by periodontal pathogens is reduced by interleukin-1 antagonists. J. Infect. Dis. 186, 511–516.

    Article  CAS  PubMed  Google Scholar 

  • Derrien T., Vaysse A., André C. and Hitte C. 2012 Annotation of the domestic dog genome sequence: finding the missing genes. Mamm. Genome 23, 124–131.

    Article  CAS  PubMed  Google Scholar 

  • Dinarello C. A. 2011 Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117, 3720–3732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Omar E. M., Carrington M., Chow W. H., McColl K. E., Bream J. H., Young H. A. et al. 2000 Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404, 398–402.

    Article  CAS  PubMed  Google Scholar 

  • Engebretson S. P., Lamster I. B., Herrera-Abreu M., Celenti R. S., Timms J. M., Chaudhary A. G. et al. 1999 The influence of interleukin gene polymorphism on expression of interleukin-1 β and tumor necrosis factor- α in periodontal tissue and gingival crevicular fluid. J. Periodontol. 70, 567–573.

    Article  CAS  PubMed  Google Scholar 

  • Genco R. J. 1992 Host responses in periodontal diseases: current concepts. J. Periodontol. 63, 338–355.

    Article  CAS  PubMed  Google Scholar 

  • Gibson R. M., Rothwell N. J. and Le Feuvre R. A. 2004 CNS injury: the role of the cytokine IL-1. Vet. J. 168, 230–237.

    Article  CAS  PubMed  Google Scholar 

  • Grantham R. 1974 Amino acid difference formula to help explain protein evolution. Science 185, 862–864.

    Article  CAS  PubMed  Google Scholar 

  • Graves D. T. and Cochran D. 2003 The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction . J. Periodontol. 74, 391–401.

    Article  CAS  PubMed  Google Scholar 

  • Johnsen A. K., Plenge R. M., Butty V., Campbell C., Dieguez-Gonzalez R., Gomez-Reino J. J. et al. 2008 A broad analysis of IL1 polymorphism and rheumatoid arthritis. Arthritis Rheum 58, 1947–1957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karimbux N. Y., Saraiya V. M., Elangovan S., Allareddy V., Kinnunen T., Kornman K. S. et al. 2012 Interleukin-1 gene polymorphisms and chronic periodontitis in adult whites: a systematic review and meta-analysis. J. Periodontol. 83, 1407–1419.

    Article  CAS  PubMed  Google Scholar 

  • Kinane D. F., Shiba H. and Hart T. C. 2005 The genetic basis of periodontitis. Periodontol. 2000 39, 91–117.

    Article  Google Scholar 

  • Kornman K. S. and di Giovine F. S. 1998 Genetic variations in cytokine expression: a risk factor for severity of adult periodontitis. Ann. Periodontol. 3, 327–338.

    Article  CAS  PubMed  Google Scholar 

  • Kornman K. S., Crane A., Wang H. Y., Giovlne F. S. D., Newman M. G., Pirk F. W. et al. 1997 The interleukin-1 genotype as a severity factor in adult periodontal disease. J. Clin. Periodontol. 24, 72–77.

    Article  CAS  PubMed  Google Scholar 

  • Kumar P., Henikoff S. and Ng P. C. 2009 Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat. Protoc. 4.7, 1073–1081.

    Article  Google Scholar 

  • Liu Y. C. G., Lerner U. H. and Teng Y. T. A. 2010 Cytokine responses against periodontal infection: protective and destructive roles. Periodontol. 2000 52, 163–206.

    Article  PubMed  Google Scholar 

  • Maccoux L. J., Salway F., Day P. J. and Clements D. N. 2007 Expression profiling of select cytokines in canine osteoarthritis tissues. Vet. Immunol. Immunopathol. 118, 59–67.

    Article  CAS  PubMed  Google Scholar 

  • Maeda S., Ohno K., Nakamura K., Uchida K., Nakashima K., Fukushima K. et al. 2012 Mucosal imbalance of interleukin-1 β and interleukin-1 receptor antagonist in canine inflammatory bowel disease. Vet. J. 194, 66–70.

    Article  CAS  PubMed  Google Scholar 

  • Masada M. P., Persson R., Kenney J. S., Lee S. W., Page R. C. and Allison A. C. 1990 Measurement of interleukin-1 α and -1 β in gingival crevicular fluid: implications for the pathogenesis of periodontal disease. J. Periodontal Res. 25, 156–163.

    Article  CAS  PubMed  Google Scholar 

  • Maksymowych W. P., Rahman P., Reeve J. P., Gladman D. D., Peddle L. and Inman R. D. 2006 Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis: an analysis of three Canadian populations. Arthritis Rheum. 54, 974–985.

    Article  CAS  PubMed  Google Scholar 

  • McGuire M. K. and Nunn M. E. 1999 Prognosis versus actual outcome. IV. The effectiveness of clinical parameters and IL-1 genotype in accurately predicting prognoses and tooth survival. J. Periodontol. 70, 49–56.

    Article  CAS  PubMed  Google Scholar 

  • Michalowicz B. S., Diehl S. R., Gunsolley J. C., Sparks B. S., Brooks C. N., Koertge T. E. et al. 2000 Evidence of a substantial genetic basis for risk of adult periodontitis. J. Periodontol. 71, 1699–1707.

    Article  CAS  PubMed  Google Scholar 

  • Morinha F., Albuquerque C., Requicha J., Dias I., Leitão J., Gut I. et al. 2012 Analysis of new lactotransferrin gene variants in a case–control study related to periodontal disease in dog. Mol. Biol. Rep. 39, 4673–4681.

    Article  CAS  PubMed  Google Scholar 

  • Morinha F., Albuquerque C., Requicha J., Dias I., Leitão J., Gut I. et al. 2011 Detection and characterization of interleukin-6 gene variants in Canis familiaris: association studies with periodontal disease. Gene 485, 139–145.

    Article  CAS  PubMed  Google Scholar 

  • Moxley G., Meulenbelt I., Chapman K., van Diujn C. M., Eline Slagboom P., Neale M. C. et al. 2010 Interleukin-1 region meta-analysis with osteoarthritis phenotypes. Osteoarthr. Cartil. 18, 200–207.

    Article  CAS  PubMed  Google Scholar 

  • Nicoll J. A., Mrak R. E., Graham D. I., Stewart J., Wilcock G., MacGowan S. et al. 2000 Association of interleukin-1 gene polymorphisms with Alzheimer’s disease. Ann. Neurol. 47, 365–368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikolopoulos G. K., Dimou N. L., Hamodrakas S. J. and Bagos P. G. 2008 Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controls. J. Clin. Periodontol. 35, 754–767.

    Article  CAS  PubMed  Google Scholar 

  • Ollier W. E., Kennedy L. J., Thomson W., Barnes A. N., Bell S. C., Bennett D. et al. 2001 Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis. Immunogenetics 53, 669–673.

    Article  CAS  PubMed  Google Scholar 

  • Papapanou P. N., Neiderud A. M., Sandros J. and Dahlén G. 2001 Interleukin-1 gene polymorphism and periodontal status. J. Clin. Periodontol. 28, 389–396.

    Article  CAS  PubMed  Google Scholar 

  • Pavlica Z., Petelin M., Juntes P., Erzen D., Crossley D. A., Skaleric U. et al. 2008 Periodontal disease burden and pathological changes in organs of dogs. J. Vet. Dent. 25, 97–105.

    Article  PubMed  Google Scholar 

  • Pihlstrom B. L., Michalowicz B. S. and Johnson N. W. 2005 Periodontal diseases. Lancet 366, 1809–1820.

    Article  PubMed  Google Scholar 

  • Preiss D. S. and Meyle J. 1994 Interleukin-1 β concentration of gingival crevicular fluid. J. Periodontol. 65, 423–428.

    Article  CAS  PubMed  Google Scholar 

  • Punzi L., Calò L. and Plebani M. 2002 Clinical significance of cytokine determination in synovial fluid. Crit. Rev. Clin. Lab. Sci. 39, 63–88.

    Article  CAS  PubMed  Google Scholar 

  • Shirodaria S., Smith J., McKay I. J., Kennett C. N. and Hughes F. J. 2000 Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1 α protein in gingival crevicular fluid of teeth with severe periodontal disease. J. Dent. Res. 79, 1864–1869.

    Article  CAS  PubMed  Google Scholar 

  • Short A. D., Catchpole B., Kennedy L. J., Barnes A., Fretwell N., Jones C. et al. 2007 Analysis of candidate susceptibility genes in canine diabetes. J. Hered. 98, 518–525.

    Article  CAS  PubMed  Google Scholar 

  • Soller J. T., Escobar H. M., Janssen M., Fork M., Bullerdiek J. and Nolte I. 2006 Cytokine genes single nucleotide polymorphism (SNP) screening analyses in canine malignant histiocytosis. Anticancer Res. 26, 3417–3420.

    CAS  PubMed  Google Scholar 

  • Soller J. T., Murua-Escobar H., Willenbrock S., Janssen M., Eberle N., Bullerdiek J. et al. 2007 Comparison of the human and canine cytokines IL-1 (α/ β) and TNF- α to orthologous other mammalians. J. Hered. 98, 485–490.

    Article  CAS  PubMed  Google Scholar 

  • Stabholz A., Soskolne W. A. and Shapira L. 2010 Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis. Periodontol. 2000 53, 138–153.

    Article  Google Scholar 

  • Szklarczyk D., Franceschini A., Kuhn M., Simonovic M., Roth A., Minguez P. et al. 2011 The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39, D561–D568.

    Article  CAS  PubMed  Google Scholar 

  • Taylor J. J., Preshaw P. M. and Donaldson P. T. 2004 Cytokine gene polymorphism and immunoregulation in periodontal disease. Periodontology 2000 35, 158–182.

    Article  PubMed  Google Scholar 

  • Yoshie H., Kobayashi T., Tai H. and Galicia J. C. 2007 The role of genetic polymorphisms in periodontitis. Periodontol. 2000 43, 102–132.

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the Veterinary Teaching Hospital of the University of Trás-os-Montes e Alto Douro in Vila Real and to the association for abandoned animal’s protection–Cantinho dos Animais Abandonados in Viseu, Portugal, for their collaboration in the samples collection. This work was partially supported by the Ph.D. individual grants SFRH/BD/44490/2008 and SFRH/ BD/44143/2008 of the Science and Technology Foundation from Portugal.

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Authors and Affiliations

  1. Department of Genetics and Biotechnology, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, P. O. Box 1013, 5000-801, Vila Real, Portugal

    C. ALBUQUERQUE, F. MORINHA, J. MAGALHÃES, H. GUEDES-PINTO & E. BASTOS

  2. Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, P. O. Box 1013, 5000-801, Vila Real, Portugal

    C. ALBUQUERQUE, J. REQUICHA, I. DIAS & C. VIEGAS

  3. Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, P. O. Box 1013, 5000-801, Vila Real, Portugal

    F. MORINHA, I. DIAS & C. VIEGAS

  4. 3B’s Research Group–Biomaterials, Biodegradables and Biomimetics, ICVS/3B’s–PT Government Associate Laboratory, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017, Barco GMR, Portugal

    I. DIAS & C. VIEGAS

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  1. C. ALBUQUERQUE
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  2. F. MORINHA
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  3. J. MAGALHÃES
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[Albuquerque C., Morinha F., Magalhães J., Requicha J., Dias I., Guedes-Pinto H., Bastos E. and Viegas C. 2015 Variants in the interleukin-1 alpha and beta genes, and the risk for periodontal disease in dogs. J. Genet. 94, xx–xx]

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ALBUQUERQUE, C., MORINHA, F., MAGALHÃES, J. et al. Variants in the interleukin-1 alpha and beta genes, and the risk for periodontal disease in dogs. J Genet 94, 651–659 (2015). https://doi.org/10.1007/s12041-015-0576-z

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