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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 periodontitis lesions
Author(s) -
Repeke Carlos Eduardo,
Trombone Ana Paula Favaro,
Ferreira Jr. Samuel B.,
Cardoso Cristina R.,
Silveira Elcia Maria,
Martins Jr. Walter,
Trevilatto Paula Cristina,
Silva João Santana,
Campanelli Ana Paula,
Garlet Gustavo Pompermaier
Publication year - 2009
Publication title -
journal of clinical periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.456
H-Index - 151
eISSN - 1600-051X
pISSN - 0303-6979
DOI - 10.1111/j.1600-051x.2009.01447.x
Subject(s) - treponema denticola , mmp1 , single nucleotide polymorphism , snp , genotype , periodontitis , porphyromonas gingivalis , chronic periodontitis , matrix metalloproteinase , biology , immunology , medicine , gene expression , genetics , gene
Aims: Our objective was to evaluate the association between the MMP1‐1607 single‐nucleotide polymorphism (SNP), periodontopathogens and inflammatory cytokines with matrix metalloproteinase‐1 (MMP‐1) mRNA levels in vitro and in vivo. Materials and Methods: This study investigated the influence of genetic ( MMP1‐1607 SNP), microbial ( Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Actinobacillus actinomycetemcomitans ) and inflammatory [tumour necrosis factor‐ α (TNF‐ α ) and interleukin‐1 β (IL‐1 β )] factors on the determination of MMP‐1 mRNA levels in periodontal tissues of non‐smoker chronic periodontitis (CP, N =178) and control (C, N =190) groups. The effects of single and repeated lipopolysaccharide (LPS) and inflammatory cytokine stimulation of macrophages with distinct MMP1‐1607 SNP genotypes were also investigated. Results: In healthy tissues, the MMP1‐1607 2G allele was associated with higher MMP‐1 levels while in CP MMP‐1 levels were associated with the presence and load of periodontopathogens, and also with TNF‐ α and IL‐1 β expression irrespective of the MMP1‐1607 genotype. In vitro data demonstrate that in 2G macrophages low‐ and intermediate‐dose LPS and TNF‐ α +IL‐1 β stimulation was associated with increased MMP‐1 expression, while strong and repeated stimulation resulted in higher MMP‐1 levels irrespective of the MMP1‐1607 genotype. Conclusion: Our data demonstrate a limited role for MMP1‐1607 SNP in periodontitis, where the extensive chronic antigenic challenge exposure overcomes the genetic control and plays a major role in the determination of MMP‐1 expression.