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

Mohammad Asgharzadeh; Nima Najafi-Ghalehlou; Behroz M Poor; Vahid Asgharzadeh; Mahya Pourostadi; Ali Vegari; Hossein S Kafil; Manouchehr Fadaee; Mehdi Farhoudi; Jalil Rashedi

doi:10.2174/1871530320666200505123443

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

Endocr Metab Immune Disord Drug Targets. 2021;21(3):520-525. doi: 10.2174/1871530320666200505123443.

Affiliations

¹ Biotechnology Research Center and Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran.
² Department of Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran.
³ Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
⁴ Department of Medical Physics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
⁵ Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
⁶ Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
⁷ Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

PMID: 32368988
DOI: 10.2174/1871530320666200505123443

Abstract

Background: Cytokines are polypeptides that play critical roles in immune responses. Gene polymorphisms occurring in the inflammatory cytokines are taking a 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 the 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.

Keywords: Iran; Single nucleotide polymorphism; azeri population; interferon gamma; multiple sclerosis; tumor necrosis factor.

MeSH terms

Case-Control Studies
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Interferon-gamma / genetics*
Iran / epidemiology
Multiple Sclerosis / diagnosis
Multiple Sclerosis / ethnology
Multiple Sclerosis / genetics*
Multiple Sclerosis / immunology
Polymorphism, Single Nucleotide*
Risk Assessment
Risk Factors
Tumor Necrosis Factor-alpha / genetics*

Substances

IFNG protein, human
TNF protein, human
Tumor Necrosis Factor-alpha
Interferon-gamma