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  • Title: Association of polymorphism -308G/A in tumor necrosis factor-alpha gene (TNF-α) and TNF-α serum levels in patients with relapsing-remitting multiple sclerosis.
    Author: Grigorova AA, Trenova AG, Stanilova SA.
    Journal: Neurol Res; 2021 Apr; 43(4):291-298. PubMed ID: 33252003.
    Abstract:
    TNF-α is an important cytokine of the inflammatory response involved in the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). The aim of this study is to explore the association between the promoter polymorphism -308G/A in the TNF-α gene (rs1800629) with genetic susceptibility to RRMS.Methods: A group of 183 RRMS patients and 169 age and gender-matched healthy controls were enrolled in the study. Genotyping of the polymorphism was performed by PCR-restriction fragment length polymorphism and quantification of TNF-α serum levels was conducted by ELISA.Results: The genotype distribution in female patients showed a significantly elevated frequency of heterozygotes (AG) (23.5% vs. 12.8%, OR = 2.072, p = 0.029) in comparison with the healthy women. Substantially higher TNF-α serum levels were observed in females compared to males, in both patients and healthy controls (p < 0.05). According to the genotype, TNF-α levels in the RRMS group were calculated in the following order: for GA/AA genotypes (5.67pg/ml vs. 3.48pg/ml, p = 0.0031) and for GG genotypes (4.58pg/ml vs. 3.52pg/ml, p = 0.00043). Moreover, the carriers of at least one A-allele of -308G/A TNF-α polymorphism (GA+AA) are significantly associated with two fold increased risk for RRMS development (OR = 1.950; p = 0.042) in women in contrast to men as well as associated with early onset of the disease (OR = 2.400; p = 0.021).Conclusion: Our study showed that the level of TNF-α in the serum of patients with RRMS showed a significant association with the -308G/A TNF-α polymorphism and gender dependency.
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