ASSESSING MIRNA-21 EXPRESSION AND CHECKPOINT PROTEIN POLYMORPHISMS IN ULCERATIVE COLITIS PATHOPHYSIOLOGY

Abstract

Background: Ulcerative Colitis (UC) Is A Chronic Autoimmune Disease With Intestinal Mucosal Inflammation And Ulceration. It Is Associated With An Annual Increase In Incidence, Underscoring The Need For Valid Biomarkers For Proper Diagnosis And Therapeutic Management.

Objective: The Present Case-Control Study Was Planned To Evaluate The Diagnostic And Prognostic Value Of Serum Mirna-21 Expression And The Correlation With The CTLA-4 (-318C/T, Rs5742909) Gene Polymorphism In The Population With UC.

Methods: One Hundred Eighty Were Recruited, Including 120 Patients With UC And 60 Ostensibly Healthy Controls. Serum Levels Of CTLA-4 And Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (Panca) Were Analysed By Enzyme-Linked Immunosorbent Assay (ELISA), And Mirna21 Expression Was Analysed By Real-Time Quantitative Polymerase Chain Reaction (RT-Qpcr). CTLA-4 Genotyping Was Done Using The Tetra-Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS-PCR).

Results: The Results Indicated A Significantly Higher Serum Mirna-21 Concentration In UC Patients Compared To Controls (8.59 ± 2.45 Vs 1.02 ± 0.21; P = 0.0001). Receiver Operating Characteristic (ROC) Curve Analysis Showed Excellent Diagnostic Performance For Mirna-21, With 100% Sensitivity And Specificity. Moreover, Mirna-21 Levels Increased With Disease Severity, With The Highest Concentrations In Severe Cases, And Were Significantly Elevated In Patients With Aggressive Disease Compared With Those With Inactive Disease. Higher Mirna-21 Levels Were Also Observed In Panca-Positive Than In Panca-Negative Patients (P=0.0001), Suggesting A Possible Association With Immune Activity.  In Contrast, No Significant Correlation Between Serum Mirna-21 Expression And CTLA-4 Genotypes (CC, CT, TT) Was Found. In Addition, The CTLA-4 (-318C/T) Polymorphism Was Not Associated With UC Susceptibility Under Any Genetic Model (Codominant, Dominant, Or Allelic).

Conclusion: Serum Mirna-21 Is A Highly Specific And Sensitive Diagnostic Biomarker Of Ulcerative Colitis, Reflecting Disease Severity And Activity. However, Mirna-21 Expression Seems To Be Independent Of Genetic Variation At The CTLA-4 Rs5742909 Locus.