IFN-γ and TNF-α Gene Polymorphisms in Multiple Sclerosis Patients in Northwest Iran

Abstract

Background: Cytokines are polypeptides that play critical roles in immune responses. Gene polymorphisms occurring in the inflammatory cytokines are taking role in autoimmune diseases, including multiple sclerosis (MS), which may induce inappropriate immune responses. Objective: The aim of this study was to investigate the allelic and genotypic frequencies of interferon gamma gene (IFN-γ) at +874A/T locus and tumor necrosis factor (TNF-α) at+308A/G locus in MS patients of Azeri population. Methods: At first, a questionnaire was prepared for each of 240 healthy, non-relative, and 152 Azeri MS patients before obtaining the blood sample from all subjects. After DNA extraction, the frequency of alleles and genotypes of the IFN-γ and TNF-α genes at +874A/T and -308G/A loci, respectively, were determined by allele-specific PCR method. Finally, the frequencies were compared between control and MS patients by chi-square test (x2 -test) and p<0.05 was considered significant. Results: In the IFN-γ +874A/T gene single nucleotide polymorphism (SNP), the most allelic and genotypic frequencies in MS patients were the A allele, 55.26% (p=0.04) and the AT genotype, 52.63% (p=0.048). In healthy individuals, it was 65.42% for the A allele and 45.42% for the AA genotype. For the TNF-α 308 G/A SNP, the highest allelic and genotypic frequencies in MS patients were the G allele with 55.92% (p<0.001) and AG genotype with 61.84%, and in healthy subjects, the allelic and genotypic frequencies were 84.2% and 70.8% for the G allele and GG genotype, respectively. Conclusion: Head trauma, the infection with herpes virus and Mycoplasma pneumonia, frequent colds and high consumption of canned foods provide grounds for MS. The T allele in the IFN-γ gene (+874) and the genotypes of AA and AG at the TNF-α gene (-308) at the position-308 were considered as potential risk factors for MS. Therefore, the polymorphisms in cytokine genes and following changes in their expression levels can be effective in susceptibility to MS.

New Insights into Risk Genes and Their Candidates in Multiple Sclerosis

“…Infection with the herpes virus and Mycoplasma pneumonia create grounds for MS. The T allele in the IFNγ gene (+874) and the genotypes of AA and AG at the TNFα gene (-308) at position−308 were considered potential risk factors for MS ( Figure 1 ) [ 57 ]. Despite GWASs explaining that there are common SNPs associated with various diseases, known common variants only account for part of the estimated heritability of common complex diseases.…”

Impact of Genetic Polymorphisms in the Interleukin-18 and Interleukin-21 Genes on the Risk and Clinical Outcomes of Multiple Sclerosis

“…Moreover, based on meta-analyses that were conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC), about 233 genetic loci involved in genes that manage immunological functions and affect the development of MS were discovered, such as human leukocyte antigen (HLA) and cytokines (Cotsapas and Mitrovic, 2018, International Multiple Sclerosis Genetics Consortium (IMSGC), 2019). The cytokine genes are characterized by the existence of genetic parameters like single nucleotide polymorphisms (SNPs) in key regions like regulatory sequences or promoter regions, which are consequently linked to elevating or declining of the cytokine level, triggering the disease-associated cytokine imbalance, and accordingly modifying the susceptibility to autoimmune diseases, including MS (Asgharzadeh et al, 2021, Bakr et al, 2021, Barac et al, 2022.…”