Dataset Information

MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements.

ABSTRACT: In this study, we evaluated the association between the MMP1-1607 polymorphism (rs1799750) and pro-inflammatory milieu elements with MMP-1 mRNA levels in vivo.MMP1-1607 SNP and the mRNA levels of MMP-1, TNF-a, IFN-g, IL-17A, IL-21, IL-10, IL-4, IL-9, and FOXp3 were determined via RealTimePCR in DNA/RNA samples from patients presenting periapical granulomas (N=111, for both genotyping and expression analysis) and control subjects (N=214 for genotyping and N=26 for expression analysis). The Shapiro-Wilk, Fisher, Pearson, Chi-square ordinal least squares regression tests were used for data analysis (p<0.05 was considered statistically significant).The MMP1-1607 1G/2G and 1G/2G+2G/2G genotypes were significantly more prevalent in the patients than in controls, comprising a risk factor for periapical lesions development. MMP-1 mRNA levels were higher in periapical lesions than in healthy periodontal ligament samples, as well as higher in active than in inactive lesions. The polymorphic allele 2G carriers presented a significantly higher MMP-1 mRNA expression when compared with the 1G/1G genotype group. The ordered logistic regression demonstrated a significant correlation between the genetic polymorphism and the expression levels of MMP-1. Additionally, the pro- and anti-inflammatory cytokines IL-17A, IFN-g, TNF-a, IL-21, IL-10, IL-9, and IL-4 were significant as complementary explanatory variables of MMP-1 expression.The MMP1-1607 SNP was identified as a risk factor for periapical lesions development, possibly due to its association with increased MMP-1 mRNA levels in periapical lesions. The MMP-1 expression is also under the control of the inflammatory milieu elements, being the cytokines TNF-a, IL-21, IL-17A, and IFN-g associated with increased MMP-1 levels in periapical lesions, while IL-10, IL-9, or IL-4 presented an inverse association.

SUBMITTER: Trombone AP

PROVIDER: S-EPMC4990366 | biostudies-literature | 2016 Jul-Aug

REPOSITORIES: biostudies-literature

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MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements.

Trombone Ana Paula Favaro AP Cavalla Franco F Silveira Elcia Maria Varize EM Andreo Camile Bermejo CB Francisconi Carolina Favaro CF Fonseca Angélica Cristina AC Letra Ariadne A Silva Renato Menezes RM Garlet Gustavo Pompermaier GP

Journal of applied oral science : revista FOB 20160701 4

<h4>Objective</h4>In this study, we evaluated the association between the MMP1-1607 polymorphism (rs1799750) and pro-inflammatory milieu elements with MMP-1 mRNA levels in vivo.<h4>Material and methods</h4>MMP1-1607 SNP and the mRNA levels of MMP-1, TNF-a, IFN-g, IL-17A, IL-21, IL-10, IL-4, IL-9, and FOXp3 were determined via RealTimePCR in DNA/RNA samples from patients presenting periapical granulomas (N=111, for both genotyping and expression analysis) and control subjects (N=214 for genotypin ...[more]

PMID: 27556208

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Project description:BACKGROUND: MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development. METHODS: We identified all eligible studies in the electronic databases of PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar (from January 2000 to June 2012). A meta-analysis was performed to evaluate the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC by calculating odds ratios (OR) and 95% confidence interval (CIs). RESULTS: Twelve studies were included in this meta-analysis. In overall comparison, significant associations were found using the recessive and allelic contrast models (OR, 1.38; 95% CI, 1.07-1.79 and OR, 1.27; 95% CI, 1.05-1.53, respectively), but no association was detected using the dominant model. In the stratified analyses by several variables, significant associations were observed using the recessive, dominant, and allelic contrast models in the Asian population (OR, 1.64; 95% CI, 1.29-2.08; OR, 1.39; 95% CI, 1.06-1.82; and OR, 1.41; 95% CI, 1.21-1.65, respectively), European population (OR, 0.58; 95% CI, 0.40-0.84; OR, 0.64; 95% CI, 0.44-0.92; and OR, 0.68; 95% CI, 0.54-0.85, respectively), and population-based subgroup (OR, 1.24; 95% CI,1.05-1.47; OR,1.48; 95% CI,1.04-2.12; and OR, 1.22; 95% CI, 1.07-1.38, respectively). Furthermore, significant associations were detected in oral cavity cancer and nasopharyngeal cancer under the recessive model. CONCLUSION: Our results suggest that the MMP1 -1607 1G>2G polymorphism is associated with risk of HNC and that it plays different roles in Asian and European populations. Further studies with large sample size are needed to validate our findings.

Project description:BackgroundOsteoarthritis (OA) is a common disease characterized by articular cartilage degeneration and secondary hyperosteogenesis. Genetic factors are associated with the occurrence of OA. While several studies have shown that the matrix metalloproteinase-1- (MMP-1-) 1607 1G/2G (rs1799750) polymorphism may be related to the occurrence and development of OA, there is inconsistency in the literature. To better estimate the relationship between the MMP-1 gene polymorphism and OA, a comprehensive meta-analysis of relevant literature was carried out.ResultsIn total, seven studies comprising 1245 OA patients and 1230 controls were included in this meta-analysis. The combined results revealed no significant association between the MMP-1-1607 1G/2G polymorphism and risk of OA in the five genetic models. However, after Bonferroni correction, the results of subgroup analysis revealed a significant correlation between the MMP-1-1607 1G/2G polymorphism and OA susceptibility in the temporomandibular joint (TMJ) OA subgroup (allelic: 2G vs. 1G: OR = 1.575, 95%CI = 1.259-1.972, P < 0.01; recessive: 2G2G vs. 1G1G+1G2G: OR = 2.411, 95%CI = 1.658-3.504, P < 0.01; and homozygote: 2G2G vs. 1G1G: OR = 2.313, 95%CI = 1.341, 3.991, P = 0.003), the younger subgroup (aged less than 60 years; allelic: 2G vs. 1G: OR = 1.635, 95%CI = 1.354, 1.974, P < 0.01; dominant: 2G1G+2G2G vs. 1G1G: OR = 1.622, 95%CI = 1.158, 2.271, P = 0.005; recessive: 2G2G vs. 1G1G+1G2G: OR = 2.209, 95%CI = 1.718, 2.840, P < 0.01; and homozygote: 2G2G vs. 1G1G: OR = 2.578, 95%CI = 1.798, 3.696, P < 0.01), the larger subgroup (N > 300), and the hospital-based case-control study (HCC) subgroup. The sensitivity analysis suggested that the results of the meta-analysis were stable and reliable. Begg's funnel plot and Egger's test indicated that there was no publication bias in this study.ConclusionOur meta-analysis indicated that although the MMP-1-1607 1G/2G polymorphism was not significantly associated with OA susceptibility among the whole sample, it played a key role in the etiology and development of TMJ OA and OA in people aged less than 60 years.

Project description:Gingival fibroblast-mediated extracellular matrix remodelling is implicated in the pathogenesis of periodontitis, yet the stimuli that regulate this response are not fully understood. The immunoregulatory adipokine leptin is detectable in the gingiva, human gingival fibroblasts express functional leptin receptor mRNA and leptin is known to regulate extracellular matrix remodelling responses in cardiac fibroblasts. We therefore hypothesised that leptin would enhance matrix metalloproteinase secretion in human gingival fibroblasts.We used in vitro cell culture to investigate leptin signalling and the effect of leptin on mRNA and protein expression in human gingival fibroblasts. We confirmed human gingival fibroblasts expressed cell surface leptin receptor, found leptin increased matrix metalloproteinase-1, -3, -8 and -14 expression in human gingival fibroblasts compared to unstimulated cells, and observed that leptin stimulation activated MAPK, STAT1/3 and Akt signalling in human gingival fibroblasts. Furthermore, leptin synergised with IL-1 or the TLR2 agonist pam2CSK4 to markedly enhance matrix metalloproteinase-1 and -3 production by human gingival fibroblasts. Signalling pathway inhibition demonstrated ERK was required for leptin-stimulated matrix metalloproteinase-1 expression in human gingival fibroblasts; whilst ERK, JNK, p38 and STAT3 were required for leptin+IL-1- and leptin+pam2CSK4-induced matrix metalloproteinase-1 expression. A genome-wide expression array and gene ontology analysis confirmed genes differentially expressed in leptin+IL-1-stimulated human gingival fibroblasts (compared to unstimulated cells) were enriched for extracellular matrix organisation and disassembly, and revealed that matrix metalloproteinase-8 and -12 were also synergistically upregulated by leptin+IL-1 in human gingival fibroblasts.We conclude that leptin selectively enhances the expression and secretion of certain matrix metalloproteinases in human gingival fibroblasts, and suggest that gingival fibroblasts may have an ECM-degrading phenotype during conditions of hyperleptinaemia (e.g., obesity, type 2 diabetes mellitus, exogenous leptin therapy).

Dataset Information

MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements.

Publications

MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements.

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