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唾液中基质金属蛋白酶(MMP)-9 和基质金属蛋白酶组织抑制剂(TIMP)-1 水平:与牙周状况及 MMP-9(-1562C/T)基因启动子多态性关系的初步研究

Salivary levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1: a pilot study about the relationship with periodontal status and MMP-9(-1562C/T) gene promoter polymorphism.

机构信息

POPCAD Research Group, Laboratory of Immunodetection and Bioanalysis, Faculty of Dentistry, University of Antioquia, Medellín, Colombia.

出版信息

Arch Oral Biol. 2011 Apr;56(4):401-11. doi: 10.1016/j.archoralbio.2010.10.021. Epub 2010 Nov 20.

Abstract

OBJECTIVE

Chronic periodontitis (CP) has been linked with an imbalance in the MMP-9/TIMP-1 ratio. A reasonable biologic explanation for this link is that the MMP-9 transcriptional activity can be modulated by MMP-9(-1562C/T) gene promoter polymorphism contributing to periodontal breakdown. This study aimed to assess the relationship between salivary MMP-9/TIMP-1 balance, MMP-9(-1562C/T) genotype and periodontal clinical status.

DESIGN

Sixty-nine CP subjects and 54 healthy controls (HC) were selected. Periodontal status was assessed by criteria based on probing depth, clinical attachment level, extent, and severity of periodontal breakdown. Salivary levels of MMP-9 and TIMP-1 were analysed using ELISA and MMP-9(-1562C/T) genotype using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between salivary levels of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio with CP was assessed individually and adjusted for confounding using a binary logistic regression model.

RESULTS

Significantly higher levels of both markers and their ratios were detected in the CP group in comparison to healthy controls. Synchronously, weak-to-moderate positive significant correlations between salivary biomarkers and clinical parameters were observed. After binary logistic regression analysis, salivary levels of MMP-9>20ngmL(-1), TIMP-1>64ngmL(-1) as well as MMP-9/TIMP-1 ratio >1 were independently associated with CP. Nevertheless, the MMP-9(-1562C/T) gene promoter polymorphism was not associated with the different degrees of chronic periodontitis and did not have influence on the salivary levels of biomarkers.

CONCLUSION

The findings when considered within the limitations of this study may indicate that although a dominant expression of MMP-9 over TIMP-1 in saliva might reflect the periodontal clinical status, the functional polymorphisms in the promoter of the MMP-9(-1562C/T) gene from the Colombian population are not linked neither with significant salivary MMP-9 variations in these individuals nor periodontal clinical status.

摘要

目的

慢性牙周炎(CP)与 MMP-9/TIMP-1 比值失衡有关。这种联系的一个合理的生物学解释是,MMP-9 转录活性可以通过 MMP-9(-1562C/T)基因启动子多态性来调节,从而导致牙周破坏。本研究旨在评估唾液 MMP-9/TIMP-1 平衡、MMP-9(-1562C/T)基因型与牙周临床状况之间的关系。

设计

选择 69 名 CP 患者和 54 名健康对照者(HC)。牙周状况根据探诊深度、临床附着水平、牙周破坏的程度和严重程度进行评估。使用 ELISA 分析唾液 MMP-9 和 TIMP-1 水平,使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析 MMP-9(-1562C/T)基因型。使用二元逻辑回归模型单独评估 MMP-9、TIMP-1 和 MMP-9/TIMP-1 比值与 CP 的关系,并进行混杂因素调整。

结果

CP 组中两种标志物及其比值均显著高于健康对照组。同时,观察到唾液生物标志物与临床参数之间存在弱至中度的正相关关系。经过二元逻辑回归分析,唾液 MMP-9>20ng/mL、TIMP-1>64ng/mL 以及 MMP-9/TIMP-1 比值>1 与 CP 独立相关。然而,MMP-9(-1562C/T)基因启动子多态性与慢性牙周炎的不同程度无关,也不影响生物标志物的唾液水平。

结论

考虑到本研究的局限性,这些发现可能表明,尽管唾液中 MMP-9 相对于 TIMP-1 的优势表达可能反映了牙周临床状况,但来自哥伦比亚人群的 MMP-9(-1562C/T)基因启动子的功能多态性与这些个体中 MMP-9 的显著唾液变化或牙周临床状况无关。

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