Genetic Polymorphism in Matrix Metalloproteinase 9 in Chronic Obstructive Pulmonary Disease in Sohag University Hospital.

NCT06503315 | Not Yet Recruiting

• 1 other identifier: Soh-Med-24-06-09MS
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex disease with multiple clinical presentations or phenotypes and remains a highly prevalent condition, causing significant morbidity and mortality worldwide. Chronic obstructive pulmonary disease (COPD) is the third most common cause of global mortality, affecting over 210 million individuals. Chronic obstructive pulmonary disease (COPD) is a chronic airway disease involving chronic local and systemic inflammatory changes, clinically characterized by continuous and progressive airflow obstruction with airway remodeling and lung parenchyma destruction as pathological basis. The precise molecular mechanism underlying the pathogenesis of COPD remains unclear ( Zhang J. et al., 2021). At present, it is generally believed that several risk factors are directly related to the pathogenesis of COPD, including host and environmental factors . Among environmental factors, smoking, exposure to chemicals, indoor and outdoor air pollution are risk factors for COPD. Host factors of COPD include antitrypsin-1, excessive deposition of extracellular matrix (ECM), corticosteroids, inflammatory stimuli, and metabolic imbalances . Matrix metalloproteinases (MMPs) is a family of calcium- and zinc-dependent proteinase. There are currently at least 26 subtypes that can degrade almost all extracellular matrix and basement membrane components . The MMP-9 gene is located on human chromosome 16, including 13 exons and 12 introns and its regulation mainly occurs at the transcriptional level. In the pathogenesis of COPD, MMP-9 mainly degrades the extracellular matrix and basement membrane of alveolar wall, destroying the normal structure of lung tissue. At the same time, MMP-9 also repairs the extracellular matrix and participates in respiratory tract reconstruction. In addition, MMP-9 can also participate in inflammatory response, causing inflammatory cells to accumulate in the airway, thus increasing airway responsiveness. Study found that MMP-9 is highly expressed in the lung tissues of COPD patients and leads to generation of sputum. MMPs are important in COPD. They degrade matrix proteins (elastin, collagen) during the disease progression . Therefore the analysis of MMP-9 gene polymorphism is an important starting point to explore the susceptibility to COPD. It has been found that there is a mutation from C to T at site 1562 of promoter MMP-9, which may affect the expression level of MMP-9 gene. The MMP-9-C1562T polymorphism is an important reason for the abnormal increase of MMP-9 expression level .

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Matrix metalloproteinase-9 gene polymorphism

  Matrix metalloproteinase-9 gene polymorphism by conventional PCR

  18 months

Study Arms (2)

cases group

Clinical assessment is based on the presence of symptoms (low vs. high) and the previous history of exacerbation( ECOPD) (≤ 1 moderate ECOPD in the previous year vs. more than one severe (hospitalized) ECOPD). Using these two dimensions, GOLD 2023 proposes to classify COPD patients in one of three groups (A, B, or E) .

control group

The control group includes 70 asymptomatic smokers and will be matched with cases by sex, age, smoking status, lacking chronic diseases in the respiratory system as malignancy and bronchial asthma

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

chronic respiratory symptom and signs such as cough ,breathlessness , wheeze ; forced expiratory volume in one second(FEV1)of predicted (FEV1%) less than 80 % ; the ratio of FEV1 to forced vital capacity (FVC , FEV1/ FVC)\<70 % ; FEV1reversibility after inhalation of 200g salbutamol (bronchodilator) of less than 12 % of prebronchodilator FEV1.

You may qualify if:

• chronic respiratory symptom and signs such as cough ,breathlessness , wheeze ; forced expiratory volume in one second(FEV1)of predicted (FEV1%) less than 80 % ; the ratio of FEV1 to forced vital capacity (FVC , FEV1/ FVC)\<70 % ; FEV1reversibility after inhalation of 200g salbutamol (bronchodilator) of less than 12 % of prebronchodilator FEV1.

You may not qualify if:

• Coexistence of asthma and COPD or with earlier history of bronchial asthma as well as patients who have never smoked were excluded from the study.

Sponsors & Collaborators

• Sohag University: lead

Study Sites (1)

Sohag university Hospital

Sohag, Egypt

Location

Related Publications (4)

• Agusti A, Bohm M, Celli B, Criner GJ, Garcia-Alvarez A, Martinez F, Sin DD, Vogelmeier CF. GOLD COPD DOCUMENT 2023: a brief update for practicing cardiologists. Clin Res Cardiol. 2024 Feb;113(2):195-204. doi: 10.1007/s00392-023-02217-0. Epub 2023 May 26.

  PMID: 37233751 BACKGROUND

• Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuna JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N, Martinez-Fierro ML. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2020 Dec 20;21(24):9739. doi: 10.3390/ijms21249739.

  PMID: 33419373 BACKGROUND

• Cai L, Zuo X, Ma L, Zhang Y, Xu F, Lu B. Associations of MMP9 polymorphism with the risk of severe pneumonia in a Southern Chinese children population. BMC Infect Dis. 2024 Jan 2;24(1):19. doi: 10.1186/s12879-023-08931-4.

  PMID: 38166679 BACKGROUND

• Lu Z, Coll P, Maitre B, Epaud R, Lanone S. Air pollution as an early determinant of COPD. Eur Respir Rev. 2022 Aug 10;31(165):220059. doi: 10.1183/16000617.0059-2022. Print 2022 Sep 30.

  PMID: 35948393 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Yasmeen M Ismail, demonastrator

CONTACT

01112564372; yassmin.ismaeal@med.sohag.edu.eg

Nagwa S Ahmed, professor

CONTACT

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: demonastrator at department of biochemistry ,sohag university

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 16, 2024
• Study Start: October 30, 2024
• Primary Completion: December 30, 2025
• Study Completion: February 24, 2026
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

EG (1)