Serum levels of tumor necrosis factor and TNFRSF1A gene polymorphisms in Egyptian multiple sclerosis patients: the influence on susceptibility and severity

Abstract

Introduction

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system that is caused by a complex interplay of genetic, epigenetic, and environmental factors.

Objectives

To investigate the relationship between serum levels of TNF and TNFRSF1A gene polymorphisms and their impact on the risk and severity of MS.

Methods

This case-control study included fifty patients with multiple sclerosis, both familial and non-familial, and fifty healthy matched controls. Molecular analysis of TNFRSF1A gene variants (rs1800693) was performed using TaqMan Real-Time PCR, and TNF serum levels were measured using ELISA.

Results

The frequency of the (C/C) genotype was significantly higher in patients (16 %) compared to controls (2 %). Additionally, the frequency of the (C) allele in TNFRSF1 (rs1800693) was significantly higher in patients (17 %) than in controls (2 %). The median serum TNF level was significantly higher in controls (79.99 Pg/ml, IQR: 67.39 to 434.48) compared to MS patients (67.93 Pg/ml, IQR: 57.15 to 80.79). Furthermore, the serum TNF level was significantly lower in patients with TNFSF1A gene variants C/C and C/T with a median of 56.31 Pg/ml (IQR: 48.84 to 73.9) compared to patients with TNFSF1A gene variant T/T with a median of 69.26 Pg/ml (IQR: 58.7 to 85.08). A significant negative correlation was found between serum TNF and EDSS in MS patients (r = −0.28, p value = 0.04).

Conclusion

The rs1800693 SNP (C/C) variant is a significant factor in the development of MS. Additionally, the reduced serum TNF levels observed in the carriers of the C allele may contribute to disease pathogenesis.