MMP3 and TIMP1 variants contribute to chronic periodontitis and may be implicated in disease progression.

AIM Matrix metalloproteinases (MMPs) play a key role in the tissue destruction characteristic of chronic periodontitis. The purpose of this study was to investigate the association of MMP and TIMP polymorphisms with chronic periodontitis in two populations. MATERIAL AND METHODS A total of 34 polymorphisms spanning 12 MMP and 2 TIMP genes were genotyped in 401 individuals from Brazil (99 cases with chronic periodontitis and 302 controls), and 274 individuals from the US (70 cases and 204 controls). Individuals were considered cases if presenting at least three teeth exhibiting sites of clinical attachment loss ≥ 5 mm in two different quadrants. Controls were characterized by absence of clinical attachment loss and no sites with probing depth >3 mm. MMP3 and TIMP1 mRNA expression was evaluated in healthy and diseased periodontal tissues. RESULTS TIMP1 showed association with chronic periodontitis in the Brazilian population (for rs5906435, p = 0.0004), whereas MMP3 showed association in the US population (for rs679620, p = 0.0003; and rs650108, p = 0.002) and in the Brazilian population (for rs639752, p = 0.005). MMP3 and TIMP1 mRNA expression was significantly higher in diseased tissues when compared to control tissues. CONCLUSIONS Our results further support a role for variations in MMP3 in chronic periodontitis and report a novel association with TIMP1. These genes may be considered additional candidate genes for chronic periodontitis.

[1]  E. Hsi,et al.  MMP-8 -799 C>T genetic polymorphism is associated with the susceptibility to chronic and aggressive periodontitis in Taiwanese. , 2011, Journal of clinical periodontology.

[2]  W. Loo,et al.  Association of matrix metalloproteinase (MMP-1, MMP-3 and MMP-9) and cyclooxygenase-2 gene polymorphisms and their proteins with chronic periodontitis. , 2011, Archives of oral biology.

[3]  F. Nociti,et al.  Interleukin-8 gene promoter polymorphism (rs4073) may contribute to chronic periodontitis. , 2011, Journal of periodontology.

[4]  J. Cirelli,et al.  Haplotypes in the Interleukin 8 Gene and Their Association with Chronic Periodontitis Susceptibility , 2011, Biochemical Genetics.

[5]  Arne S Schäfer,et al.  Periodontal genetics: a decade of genetic association studies mandates better study designs. , 2011, Journal of clinical periodontology.

[6]  N. Donos,et al.  Association between interleukin-6 -174 polymorphism and Aggregatibacter actinomycetemcomitans in chronic periodontitis. , 2010, Journal of periodontology.

[7]  P. Emmadi,et al.  Genetic polymorphisms in periodontal diseases: an overview. , 2010, Indian journal of dental research : official publication of Indian Society for Dental Research.

[8]  G. Garlet,et al.  Strong and persistent microbial and inflammatory stimuli overcome the genetic predisposition to higher matrix metalloproteinase-1 (MMP-1) expression: a mechanistic explanation for the lack of association of MMP1-1607 single-nucleotide polymorphism genotypes with MMP-1 expression in chronic periodont , 2009, Journal of clinical periodontology.

[9]  P. Söder,et al.  Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in blood as markers for early atherosclerosis in subjects with chronic periodontitis. , 2009, Journal of periodontal research.

[10]  G. Garlet,et al.  Differential patterns of receptor activator of nuclear factor kappa B ligand/osteoprotegerin expression in human periapical granulomas: possible association with progressive or stable nature of the lesions. , 2008, Journal of endodontics.

[11]  B. Rai,et al.  Biomarkers of periodontitis in oral fluids. , 2008, Journal of oral science.

[12]  J. Granjeiro,et al.  MMP gene polymorphisms as contributors for cleft lip/palate: association with MMP3 but not MMP1. , 2007, Archives of oral biology.

[13]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[14]  H. Müller,et al.  A combination of alleles 2 of interleukin (IL)-1A−889 and IL-1B+3954 is associated with lower gingival bleeding tendency in plaque-induced gingivitis in young adults of Arabic heritage , 2007, Clinical Oral Investigations.

[15]  H. Bağcı,et al.  Association of interleukin-10 gene polymorphisms with severe generalized chronic periodontitis. , 2007, Journal of periodontology.

[16]  Leo Tjäderhane,et al.  The role of matrix metalloproteinases in the oral environment , 2007, Acta odontologica Scandinavica.

[17]  M. C. Santos,et al.  Genetic polymorphisms in the MMP-1 and MMP-3 gene may contribute to chronic periodontitis in a Brazilian population. , 2006, Journal of clinical periodontology.

[18]  A. Viera,et al.  Understanding interobserver agreement: the kappa statistic. , 2005, Family medicine.

[19]  D. Kinane,et al.  The potential role of interleukin-17 in the immunopathology of periodontal disease. , 2005, Journal of clinical periodontology.

[20]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[21]  G. Garlet,et al.  Matrix metalloproteinases, their physiological inhibitors and osteoclast factors are differentially regulated by the cytokine profile in human periodontal disease. , 2004, Journal of clinical periodontology.

[22]  V. Znojil,et al.  Genetic variations in the matrix metalloproteinase-1 promoter and risk of susceptibility and/or severity of chronic periodontitis in the Czech population. , 2004, Journal of clinical periodontology.

[23]  M. Javadi,et al.  NF-kappaB binds to a polymorphic repressor element in the MMP-3 promoter. , 2004, Biochemical and biophysical research communications.

[24]  B. Haye,et al.  TIMPs as multifacial proteins. , 2004, Critical reviews in oncology/hematology.

[25]  Gary C Armitage,et al.  Periodontal diagnoses and classification of periodontal diseases. , 2004, Periodontology 2000.

[26]  S. Takashiba,et al.  Tumor necrosis factor-alpha gene (TNF-alpha) -1031/-863, -857 single-nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese. , 2003, Journal of clinical periodontology.

[27]  M. Nunn.  Understanding the etiology of periodontitis: an overview of periodontal risk factors. , 2003, Periodontology 2000.

[28]  John P A Ioannidis,et al.  Genetic associations: false or true? , 2003, Trends in molecular medicine.

[29]  R. Scarel-Caminaga,et al.  MMP-1 promoter polymorphism: association with chronic periodontitis severity in a Brazilian population. , 2003, Journal of clinical periodontology.

[30]  G. Godeau,et al.  Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy and diseased human gingiva. , 2003, Journal of periodontology.

[31]  N Risch,et al.  High-throughput genotyping with single nucleotide polymorphisms. , 2001, Genome research.

[32]  J. Haines,et al.  Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. , 1997, JAMA.

[33]  J. Haines,et al.  Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis , 1997 .

[34]  T. Hart,et al.  Genetic factors in the pathogenesis of periodontitis. , 1997, Periodontology 2000.

[35]  Y. Konttinen,et al.  Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and saliva of periodontitis patients. , 1996, Journal of clinical periodontology.

[36]  H. Larjava,et al.  Matrix Metalloproteinases (MMP-2 and MMP-9) of the Oral Cavity: Cellular Origin and Relationship to Periodontal Status , 1994, Journal of dental research.

[37]  C. McCulloch,et al.  Gingival crevicular fluid gelatinase and its relationship to periodontal disease in human subjects. , 1992, Journal of periodontal research.

[38]  A. Letra,et al.  IL8 Gene Promoter Polymorphism (rs4073) may Contributes to Chronic Periodontitis , 2011 .

[39]  K. Brew,et al.  The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. , 2010, Biochimica et biophysica acta.

[40]  M. Nagata,et al.  Altered gene expression levels of matrix metalloproteinases and their inhibitors in periodontitis-affected gingival tissue. , 2008, Journal of periodontology.

[41]  M. Kurzawski,et al.  Polymorphism in interleukin-1beta gene and the risk of periodontitis in a Polish population. , 2006, Advances in medical sciences.

[42]  Pak Chung Sham,et al.  Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits , 2003, Bioinform..

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