MMP-3(-1171 5A/6A;Lys45Glu) 变体影响基质金属蛋白酶 (MMP)-3 的血清水平，并与 COPD 的严重程度相关：突尼斯人群中 MMP-3、MMP-7 和 MMP-12 的研究。

MMP-3 (-1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)-3 and correlate with severity of COPD: A study of MMP-3, MMP-7 and MMP-12 in a Tunisian population.

机构信息

Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire 'Biologie, Médecine et Santé', Université de Sousse, Faculté de Médecine de Sousse, Tunisia.

Department of Biology, Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Tunisia.

出版信息

J Gene Med. 2018 Jan;20(1). doi: 10.1002/jgm.2999. Epub 2017 Dec 29.

DOI:10.1002/jgm.2999

PMID:29165854

Abstract

BACKGROUND

The present study aimed to examine the role of matrix metalloproteinase (MMP)-3 [(-1171) 5A/6A; Lys45Glu (A/G)], MMP-7 [(-181) A/G] and MMP-12 [(-82) A/G; Asn357Ser (A/G)] variants in the development and severity of chronic obstructive pulmonary disease (COPD) in Tunisians.

METHODS

Plethysmography was performed in all participants to measure forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC parameters. Genotyping of MMP-3, MMP-7 and MMP-12 polymorphisms was carried out in 138 patients with COPD and 216 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism. Serum levels of MMPs and cytokines (interleukin-6, tumor necrosis factor-α) were determined by an enzyme-linked immunosorbent assay.

RESULTS

No significant correlations were observed between genetic variations in MMP-3, MMP-7 and MMP-12 and the risk of development of COPD. Additionally, no impact of MMP-7 (-181) A/G and MMP-12 [(-82) A/G; Asn357Ser (A/G)] polymorphisms was observed on the respective protein levels and clinical parameters of the disease. Interestingly, both MMP-3 (-1171) 5A/6A and Lys45Glu (A/G) variants were associated with respiratory function, as well as with serum levels of MMP-3 in COPD patients. A relationship was found between the (-1171) 6A and 45Glu (G) alleles of the MMP-3 gene and enhanced airflow limitation among COPD patients. Additionally, carriers of the 6A6A and 45 GG genotypes present higher MMP-3 levels than noncarriers.

CONCLUSIONS

MMP-3 (-1171) 5A/6A and Lys45Glu (A/G) polymorphisms were associated with the decline of lung function among COPD patients. These results could be linked to the upregulation of MMP-3 in serum from COPD patients carrying the (-1171) 6A and 45 G homozygous genotypes.

摘要

背景

本研究旨在探讨基质金属蛋白酶（MMP）-3 [（-1171）5A/6A；Lys45Glu（A/G）]、MMP-7 [（-181）A/G]和 MMP-12 [（-82）A/G；Asn357Ser（A/G）] 变体在突尼斯人群慢性阻塞性肺疾病（COPD）的发展和严重程度中的作用。

方法

所有参与者均进行体描法测量 1 秒用力呼气量（FEV1）、用力肺活量（FVC）和 FEV1/FVC 等参数。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对 138 例 COPD 患者和 216 例健康对照者的 MMP-3、MMP-7 和 MMP-12 多态性进行基因分型。采用酶联免疫吸附试验（ELISA）法测定 MMP 和细胞因子（白细胞介素-6、肿瘤坏死因子-α）的血清水平。

结果

MMP-3、MMP-7 和 MMP-12 的遗传变异与 COPD 发病风险之间无显著相关性。此外，MMP-7（-181）A/G 和 MMP-12 [（-82）A/G；Asn357Ser（A/G）] 多态性对各自的蛋白水平和疾病的临床参数也没有影响。有趣的是，MMP-3（-1171）5A/6A 和 Lys45Glu（A/G）变体均与 COPD 患者的呼吸功能以及 MMP-3 的血清水平有关。在 COPD 患者中，MMP-3 基因的（-1171）6A 和 45Glu（G）等位基因与气流受限加重有关。此外，携带 MMP-36A6A 和 45 GG 基因型的患者比非携带者的 MMP-3 水平更高。