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

ArticleinJournal Of Clinical Periodontology 40(2) · October 2012with8 Reads
Impact Factor: 4.01 · DOI: 10.1111/jcpe.12035 · Source: PubMed
Abstract

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.

    • "Our results are consistent with findings in similar diseases such as rheumatoid arthritis [43]and systemic lupus erythematus [44]. However, the contribution of MMP-9 1562 polymorphism to disease risk was significant in COPD [45], periodontitis [46] and cancers [47]. The MMP-9 1562 C/T is responsible of a substitution, which affects the affinity of a transcription repressor protein of the MMP-9 gene promoter modifying thus the transcriptional activity of MMP-9 gene. "
    [Show abstract] [Hide abstract] ABSTRACT: The human Matrix Metalloproteinases (MMPs) are importantly involved in aneurysm formation. Since the clinical manifestations in Behçet disease (BD) include aneurysm formation among major symptoms, polymorphisms in MMP-9 might be associated with BD susceptibility. The aim of the current case-control study was to investigate the association of four single nucleotide polymorphisms (SNPs) in MMP-9 gene: -1562 C/T, 2003 G/A (R668Q), 836 A/G (Q279R) and 1721 C/G (R574P) with BD risk in the Tunisian population. The distribution of MMP-9 gene polymorphisms was analyzed by polymerase chain-reaction (PCR) and restriction fragment length polymorphism (RFLP) for 240 BD patients and 288 controls. Our study indicated that the MMP-9 -1562 C/T polymorphism (rs3918242) was not associated with BD risk. We found a significant association of the MMP-9 2003 G/A (rs17577) with an increased susceptibility to BD. However, the MMP-9 1721 C/G polymorphism (rs2250889) had a protective role against the development of BD. Subgroup analysis based on stratification by gender revealed that the MMP-9 2003 G/A polymorphism was associated with a highly significant BD risk in women's group (G vs. A: P = 0.0000001). However, the MMP-9 836 A/G polymorphism had a protective role in men's group (G vs. A: P = 0.00043). The MMP-9 1721 C/G polymorphism was associated with a protective effect in both men and women groups (CG + GG vs. CC: P= 0.04 and P = 0.0002, respectively). The haplotype analysis did not show any association with BD risk. A significant difference in the MMP-9 serum levels were observed in the patient subgroup with ocular lesions manifestations.
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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. "
    [Show abstract] [Hide abstract] 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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  • [Show abstract] [Hide abstract] 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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