MMP-9-1562C > T contributes to periodontitis susceptibility

Institute of Stomatology, Nanjing Medical University, Nanjing, China.
Journal Of Clinical Periodontology (Impact Factor: 4.01). 10/2012; 40(2). DOI: 10.1111/jcpe.12035
Source: PubMed


The study was conducted to explore the potential association of Matrix metalloproteinases (MMP)-9 -1562C>T with susceptibility to periodontitis.
Electronic literature searches of PubMed, EMBASE and EBSCO databases were performed. Fixed-effects or random-effects models were used to calculate the pooled odds ratios (ORs) for four genetic comparisons.
Seven eligible studies with a total of 628 cases and 689 controls were recruited in the pooled analysis. We found MMP-9 -1562C>T contributed to decreased risk of chronic periodontitis. Furthermore, the polymorphism was associated with modified risk of periodontitis among Caucasian populations.
This study indicated that MP-9 -1562C>T might be involved in the development of periodontitis. A replication of our results in independent large analysis populations is necessary to give evidence to our observation.

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    • "These functional MMPs SNPs are associated mostly with cardiovascular disease susceptibility, but also with cancer, rheumatic diseases and other conditions, such as endometriosis161718192021222324. To our knowledge, only two papers on MMPs SNPs and infection have been published, one reporting an association of a MMP9 SNP with periodontitis susceptibility25 and a second, from our group, of a MMP1 SNP with bacterial osteomyelitis26. Very recently an association between a TIMP1 SNP and sepsis mortality has been published27. "
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    ABSTRACT: Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs), modulated by different single nucleotide polymorphisms (SNPs), are critical in sepsis development. Ninety ICU severely septic and 91 ICU uninfected patients were prospectively studied. MMP-1 (-1607 1G/2G), MMP-3 (-1612 5A/6A), MMP-8 (-799 C/T), MMP-9 (-1562 C/T), and MMP-13 (-77A/G) SNPs were genotyped. Plasma MMPs (-1, -2, -3, -8, -9, -10, -13) and TIMPs (-1,-2,-4) were measured. AA homozygotes and A allele carriers of MMP-13 (-77 A/G) and 1G2G carriers of the MMP-1 (-1607 1G/2G) SNPs frequencies were different between septic and uninfected patients (p < 0.05), as well as plasma MMP-3, -8, -9 -10 and TIMP-2 levels (p < 0.04). No differences in MMPs levels among MMP-13 or MMP-1 SNPs genotypes carriers were observed. The area under the ROC curve for MMP-8 in the diagnosis of sepsis was 0.87 (95% CI 0.82-0.92), and that of CRP was 0.98 (0.94-0.998), whereas the area of MMP-9 in the detection of non-septic state was 0.73 (0.65-0.80), p < 0.0001 for all curves. Sepsis associated with increased MMP-8 and decreased MMP-9 levels in multivariate analysis (p < 0.0002). We report for the first time an association between MMP-13 and MMP-1 SNPs and sepsis. An independent association of MMP-8 and MMP-9 levels with sepsis was also observed.
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    ABSTRACT: Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease induced by genetic and environmental factors. Gelatinases (MMP-2 and MMP-9) and their natural inhibitor TIMP-1 are active players in the inflammatory process. We aimed to determine if inheritance of specific MMP-2, MMP-9, or TIMP-1 gene polymorphisms is associated with RAS susceptibility. Ninety six RAS patients and 153 healthy controls were studied. Six polymorphisms were genotyped; rs17576, rs3918242, and rs11697325 in MMP-9, MMP2 rs2285053, and TIMP-1 rs6609533. Association was assessed by logistic regression analysis after adjustment for confounding factors. Linkage disequilibrium (LD) was assessed using the Haploview program. MMP-9 rs11697325 was significantly associated with RAS with an increase in the AA genotype in patients using χ(2) analysis (OR=2.3, P=0.006) and adjusted regression analysis (OR=3.1, P=0.009). MMP-9 rs11697325 and rs17576 showed strong LD (D=0.95), with an increase of the AA haplotype (P=0.023) and a decrease in the GA haplotype (P=0.015) in patients. This is the first study to investigate the association of MMPs or TIMP-1 with RAS. We found a significant association between MMP-9rs11697325 polymorphisms and RAS. Confirmatory studies in other populations and functional investigations are needed to determine the role of these genes in RAS. This article is protected by copyright. All rights reserved.
    Full-text · Article · Oct 2013 · Oral Diseases
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    ABSTRACT: Matrix metalloproteinase-3 (MMP3) plays a key role in tissue degradation in periodontitis. The relationship between the MMP3 -1171 5A/6A polymorphism (rs35068180) and periodontitis has been widely studied. However, existing studies have yielded contradictory results. We therefore conducted a meta-analysis to comprehensively investigate these inconclusive findings. Several electronic databases were searched for eligible articles. Seven case-control studies from 6 articles were searched without any language restrictions. Pooled estimates indicated that MMP3 -1171 5A/6A polymorphism is associated with a decreased risk of periodontitis (allelic genetic model: OR = 0.70, 95% CI: 0.62-0.80, Pheterogeneity = 0.315; heterozygous model: OR = 0.50, 95% CI: 0.39-0.65, Pheterogeneity = 0.221; homozygous model: OR = 0.42, 95% CI: 0.25-0.69, Pheterogeneity = 0.265; dominant model: OR = 0.49, 95% CI: 0.38-0.62, Pheterogeneity = 0.238, respectively). Similar results were also found in chronic periodontitis (CP), Asian, Asian&CP, and non-smokers subgroups. Moreover, MMP3 rs35068180 polymorphism might be associated with a lower risk of aggressive periodontitis (AgP) in Asians (allelic genetic model: OR = 0.66, 95% CI: 0.48-0.91, Pheterogeneity = 0.945), and CP in Caucasians and Brazilians. In conclusion, this meta-analysis demonstrates that MMP3 -1171 5A/6A polymorphism may be associated with decreased risk of both CP and AgP in Asians. Large independent studies to replicate these results are necessary to validate these associations in other populations.
    Full-text · Article · Jun 2015 · Scientific Reports
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