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Journal of Genetics

, 98:32 | Cite as

Matrix metalloproteinase gene polymorphisms in chronic periodontitis: a case–control study in the Indian population

  • Poulami MajumderEmail author
  • Sujay Ghosh
  • Subrata Kumar Dey
Research Article
  • 4 Downloads

Abstract

Chronic periodontitis (CP) is the common form of inflammatory oral disease. Matrix metalloproteinases (MMPs) play a pivotal role in the progression of CP by degrading gingival tissue and its remodelling. Here, we conducted a case–control study to investigate a possible association of single-nucleotide polymorphism of MMP genes and their interaction with CP in the Indian population. A total of 357 DNA samples of venous blood was isolated, of which 157 were identified as CP patients and 200 were healthy individuals. Genotyping of six MMP genes (MMP1, MMP3, MMP7, MMP8, MMP12 and MMP13) was done using polymerase chain reaction following Sanger’s method of sequencing. Statistical analyses were performed by SPSS v16.0, R package (SNPassoc). Gene–gene interactions were evaluated by MDR 3.0.2. The frequency of 6A allele of MMP3 \(-\)11715A-6A gene polymorphisms (36%) and G allele of MMP8 +17G-C gene polymorphisms (34%) were higher in the CP population compared with the healthy population (19% and 24%, respectively). A significant association of T allele of MMP8 \(-\)799C-T gene promoter polymorphism was found with CP (\(\hbox {OR}=2.95\), \(95\%\hbox {CI}=2.16-4.04\), \(P<0.0001\)). Genotypic frequency of MMP12 \(-\)82A-G polymorphism is associated with CP risk while its allelic distribution is not (\(\hbox {OR}=1.32\), \(95\%\hbox {CI}=0.93-1.88\), \(P=0.129\)). Gene–gene interactions show the best cross validation consistency model, i.e. MMP1 \(-\)519A-G X MMP7 \(-\)181A-G X MMP8 \(-\)799C-T polymorphisms with a value of 9/10. This gene–gene interaction shows that the significant association of MMP8 \(-\)799C-T polymorphism with CP increased susceptibility. Allelic distribution of MMP8 +17G-C and MMP3 \(-\)11715A-6A polymorphisms revealed their protective role towards decreased risk of CP. MMP1 \(-\)519A-G and MMP7 \(-\)181A-G polymorphisms show combinatorial synergistic effect on CP risk.

Keywords

chronic periodontitis matrix metalloproteinases single-nucleotide polymorphism genotype allele cross validation consistency 

Notes

Acknowledgement

We thank Dr Vineet Nair and all participants of this study. This work was supported by DBT, India (102/IFD/SAN/1699/2015–2016).

References

  1. Albander J. M. 2005 Epidemiology and risk factors for periodontal diseases. Dent. Clin. N. Am. 49, 517–532.CrossRefGoogle Scholar
  2. Astolfi C., Shinohara L., da Silva R., Santos M. C., Line S. and de Souza A. P. 2006 Genetic polymorphisms in the MMP-1 and MMP-3 gene may contribute to chronic periodontitis in a Brazilian population. J. Clin. Periodontol. 33, 699–703.CrossRefGoogle Scholar
  3. Chou Y. H., Ho Y. P., Lin Y. C., Hu K. F., Yang Y. H., Ho K. Y. et al. 2011 MMP-8 -799 C \(>\) T genetic polymorphism is associated with the susceptibility to chronic and aggressive periodontitis in Taiwanese. J. Clin. Periodontol. 38, 1078–1084.CrossRefGoogle Scholar
  4. Fontana V., Silva P., Gerlach R. and Tanus-Santos J. 2012 Circulating matrix metalloproteinases and their inhibitors in hypertension. Clin. Chim. Acta. 413, 656–662.CrossRefGoogle Scholar
  5. Gurkan A., Emingil G., Saygan B. H., Atilla G., Cinarcik S., Kose T. et al. 2008 Gene polymorphisms of matrix metalloproteinase-2, -9 and -12 in periodontal health and severe chronic periodontitis. Arch. Oral. Biol. 53, 337–345.CrossRefGoogle Scholar
  6. Hajishengallis G. 2015 Periodontitis: from microbial immune subversion to systemic inflammation. Nat. Rev. Immunol. 15, 30–44.CrossRefGoogle Scholar
  7. Holla L. I., Fassmann A., Vasku A., Goldbergova M., Beranek M., Znojil V. et al. 2005 Genetic variations in the human gelatinase A (matrix metalloproteinase-2) promoter are not associated with susceptibility to, and severity of, chronic periodontitis. J. Periodontol. 76, 1056–1060.CrossRefGoogle Scholar
  8. Holla L., Hrdlickova B., Vokurka J. and Fassmanna A. 2012 Matrix metalloproteinase 8 (MMP8) gene polymorphisms in chronic periodontitis. Arch. Oral. Biol. 57, 188–196.CrossRefGoogle Scholar
  9. Holla L., Jurajda M., Fassmann A., Dvorakova N., Znojil V. and Vacha J. 2004 Genetic variations in the matrix metalloproteinase-1 promoter and risk of susceptibility and/or severity of chronic periodontitis in the Czech population. J. Clin. Periodontol. 31, 685–690.CrossRefGoogle Scholar
  10. Itagaki M., Kubota T., Tai H., Shimada Y., Morozumi T. and Yamazaki K. 2004 Matrix metalloproteinase-1 and -3 gene promoter polymorphisms in Japanese patients with periodontitis. J. Clin. Periodontol. 31, 764–769.CrossRefGoogle Scholar
  11. Keles G., Gunes S., Sumer A., Sumer M., Kara N., Bagci H. et al. 2006 Association of matrix metalloproteinase-9 promoter gene polymorphism with chronic periodontitis. J. Periodontol. 77, 1510–1514.CrossRefGoogle Scholar
  12. Letra A., Silva R. M., Rylands R. J., Silveira E. M., de Souza A. P., Wendell S. K. et al. 2012 MMP3 and TIMP1 variants contribute to chronic periodontitis and may be implicated in disease progression. J. Clin. Periodontol. 39, 707–716.CrossRefGoogle Scholar
  13. Li G., Yue Y., Tian Y., Li J. L., Wang M., Liang H. et al. 2012 Association of matrix metalloproteinase (MMP)-1, 3, 9, interleukin (IL)-2, 8 and cyclooxygenase (COX)-2 gene polymorphisms with chronic periodontitis in a Chinese population. Cytokine 60, 552–560.CrossRefGoogle Scholar
  14. Li W., Zhu W., Singh P., Ajmera D., Song J. and Ji P. 2016 Association of common variants in MMPs with periodontitis risk. Dis. Markers 2016, 1545974.PubMedPubMedCentralGoogle Scholar
  15. Loo W. T., Wang M., Jin L. J., Cheung M. N. and Li G. R. 2011 Association of matrix metalloproteinase (MMP-1, MMP-3 and MMP-9) and cyclooxygenase-2 gene polymorphisms and their proteins with chronic periodontitis. Arch. Oral. Biol. 56, 1081–1090.CrossRefGoogle Scholar
  16. Luczyszyn S., De Souza C., Braosi A., Dirschnabel A., Claudino M., Repeke C. et al. 2012 Analysis of the association of an MMP1 promoter polymorphism and transcript levels with chronic periodontitis and end-stage renal disease in a Brazilian population. Arch. Oral. Biol. 57, 954–963.CrossRefGoogle Scholar
  17. Majumder P., Singh S. J., Nair V., Bhaumik P., Mukherjee A., Ghosh P. et al. 2017 Alliance of matrix metalloproteinase-9 (MMP-9) promoter gene polymorphism with chronic and aggressive periodontitis in Indian population. Meta Gene. 12, 88–93.CrossRefGoogle Scholar
  18. Malemud C. J. 2006 Matrix metalloproteinases (MMPs) in health and disease: an overview. Front. Biosci. 11, 1696–1701.CrossRefGoogle Scholar
  19. Molander A., Reit C., Dahlén G. and Kvist T. 1998 Microbiological status of root-filled teeth with apical periodontitis. Int. Endontic. J. 31, 1–7.CrossRefGoogle Scholar
  20. Page R. and Beck J. D. 1997 Risk assessment for periodontal diseases. Int. Dent. J. 47, 61–87.CrossRefGoogle Scholar
  21. Parmar G., Sangwan P., Vashi P., Kulkarni P. and Kumar S. 2009 Effect of chewing a mixture of areca nut and tobacco on periodontal tissues and oral hygiene status. J. Oral. Sci. 50, 57–62.CrossRefGoogle Scholar
  22. Rintakoski K., Kaprio J., Murtomaa H. 2010 Genetic and environmental factors in oral health among twins. J. Dent. Res. 89, 700–704.CrossRefGoogle Scholar
  23. Rossa C., Min L., Bronson P. and Kirkwood K. L. 2010 Transcriptional activation of MMP-13 by periodontal pathogenic LPS requires p38 MAP kinase. J. Endotoxin. Res. 13, 85–93.CrossRefGoogle Scholar
  24. Sinitsky M. Y., Minina V. I., Asanov M. A., Yuzhalin A. E., Ponasenko A. V. and Druzhinin V. G. 2017 Association of DNA repair gene polymorphisms with genotoxic stress in underground coal miners. Mutagenesis 32, 501–509.CrossRefGoogle Scholar
  25. Sorsa T., Tjäderhane L. and Salo T. 2004 Matrix metalloproteinases (MMPs) in oral diseases. Oral. Dis. 10, 311–318.CrossRefGoogle Scholar
  26. Visse R. and Nagase H. 2003 Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ. Res. 92, 827–839.CrossRefGoogle Scholar
  27. Wang B., Xu Q., Yang H., Sun L. and Yuan Y. 2016 The association of six polymorphisms of five genes involved in three steps of nucleotide excision repair pathways with hepatocellular cancer risk. Oncotarget. 7, 20357–20367.PubMedPubMedCentralGoogle Scholar
  28. Weng H., Yan Y., Jin Y. H., Meng X., Mo Y. and Zeng, X. 2016 Matrix metalloproteinase gene polymorphisms and periodontitis susceptibility: a meta-analysis involving 6,162 individuals. Sci. Rep. 6, 24812.CrossRefGoogle Scholar
  29. Zeng X., Zhang Y., Kwong J. S., Zhang C., Li S., Sun F. et al. 2015 The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J. Evid. Based. Med. 8, 2–10.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  • Poulami Majumder
    • 1
    Email author
  • Sujay Ghosh
    • 2
  • Subrata Kumar Dey
    • 1
  1. 1.Department of Biotechnology, Centre for Genetic Studies, School of Biotechnology and Biological SciencesMaulana Abul Kalam Azad University of Technology (Formerly West Bengal University of Technology)KolkataIndia
  2. 2.Cytogenetics and Genomics Research Unit, Department of ZoologyUniversity of CalcuttaKolkataIndia

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