Association Between Matrix Metalloproteinase-2 Gene Polymorphism rs243865 and Susceptibility to Cataract Development

The primary aim of this study is to investigate the potential association between MMP-2 gene polymorphism and susceptibility to cataract development in Egyptian patients. Furthermore, this study aims to compare between cataract patients and healthy controls by measuring the serum IL-6 concentration to evaluate its relationship with disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Cataract
• Intervention / Treatment: Genetic: genotyping assay by real-time PCR; Diagnostic test: ELISA

Detailed Description

Cataract is a leading cause of blindness worldwide and is more common in low socioeconomic states and developing countries. According to the WHO, among 3 million visually impaired and 1 million blind persons in Egypt, about 60% have cataract.

The lens undergoes several morphological, biochemical, and physical changes with age which are causal for the formation of age-related cataract.

Oxidative stress can directly influence the solubility of the lens proteins, which increases the lens's opacity.

some studies suggest that inflammatory response may be involved in the occurrence of catarac. and that the pathophysiology is largely attributed to peptide mediators, such as transforming growth factor-beta (TGF-β), epidermal growth factor (EGF) and matrix metalloproteinases (MMPs), with the inhibition of these and other related molecules showing promising results.

Matrix metalloproteinases (MMPs) are a kind of calcium-zinc ion-dependent proteolytic enzyme involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and are involved in several intracellular mechanisms from cell differentiation, proliferation, and angiogenesis to apoptosis.

Several studies' results suggest that the rs243865 (16q13-q21) polymorphism in the promoter region of the metalloproteinase-2 (MMP-2) gene is associated with ophthalmological disorders such as age-related macular degeneration. A recent study suggested that the MMP-2 rs243865 (C/T) polymorphism is associated with an increased risk of cataract.

The expression and activation of MMP-2 can be regulated by environmental influences from surrounding stroma, such as cytokines. some studies suggest that IL6 upregulates the expression of MMPs including MMP-2.

IL-6 is a soluble mediator with a pleiotropic effect on inflammation, immune response, and hematopoiesis. high levels of Il-6 in cataract patients may support the inflammatory response theory of disease development.

this study will follow the tenets of the Declaration of Helsinki. All study participants will sign informed written consent before enrolment in this study.

All study participants will be subjected to complete ophthalmic examination including slit-lamp and fundus examinations. Detailed medical history will be taken.

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

• Study Contact: Name: Tasneem Ahmed; Phone Number: 01122745410; Email: tasneemsayed@med.sohag.edu.eg
• Study Contact Backup: Name: Alshimaa Abdelall; Phone Number: 01090096575

Study Locations

• Egypt
  • Sohag, Egypt, 82519
    • faculty of medicine Sohag university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

cataractous patients in Department of ophthalmology in Sohag University Hospitals and healthy controls of matched age and sex

Description

Inclusion Criteria:

• Group A (control group) will include 30 eyes of 30 normal healthy non-cataractous volunteers aged ≥21 years. Group B (experimental group 1) will include 30 eyes of 30 cataractous patients aged >50 years and diagnosed with senile cataract. Group C (experimental group 2) will include 30 eyes of 30 cataractous patients aged ≥21 to 50 years and diagnosed with secondary cataract. The control group will include participants who will be age-matched and sex-matched with the patients in the experimental groups

Exclusion Criteria:

• concomitant eye pathology or inflammation, systemic diseases and previous eye or systemic surgery.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control group (GroupA); normal healthy non-cataractous volunteers aged ≥21 years	Genetic: genotyping assay by real-time PCR; genotyping assay of MMP-2 gene with the real-time polymerase chain reaction; Diagnostic test: ELISA; . IL-6 level in serum will be analyzed by ELISA assay kit.
Group B (experimental group 1); cataractous patients aged >50 years and diagnosed with senile cataract.	Genetic: genotyping assay by real-time PCR; genotyping assay of MMP-2 gene with the real-time polymerase chain reaction; Diagnostic test: ELISA; . IL-6 level in serum will be analyzed by ELISA assay kit.
Group C (experimental group 2); cataractous patients aged ≥21 to 50 years and diagnosed with secondary cataract	Genetic: genotyping assay by real-time PCR; genotyping assay of MMP-2 gene with the real-time polymerase chain reaction; Diagnostic test: ELISA; . IL-6 level in serum will be analyzed by ELISA assay kit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MMP-2 gene (rs243865) polymorphism in cataract patients and healthy controls	Matrix Metalloproteinase-2 Gene Polymorphism using real-time PCR	1 year maximum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
compare between cataract patients and healthy controls by measuring the serum IL-6 concentration to evaluate its relationship with disease.	measure serum levels of IL-6 by ELISA	1 year maximum

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• Dong Y, Mu GY, Chen F, Zhao RL, Wang M, Wang B. Correlation between MMP-2 gene polymorphism and cataract susceptibility. Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3167-3172. doi: 10.26355/eurrev_201904_17674.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: December 31, 2022
• First Posted (Actual): January 4, 2023

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: December 31, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Lens Diseases; Cataract
• Other Study ID Numbers: Soh-Med-22-12-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No