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Myxovirus resistance protein A (MxA) polymorphism is associated with IFNβ response in Iranian multiple sclerosis
Arezou Sayad1, Soudeh Ghafouri-Fard1, Mir Davood Omrani1,2
1Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Multiple sclerosis (MS) is a heterogeneous immune-related demyelinating disorder of central nervous system with several genetic and environmental factors contributing in its pathogenesis or patients' response to therapies. Myxovirus resistance protein A (MxA) is among the genes which are induced by IFNβ and are involved in the MS pathogenesis and/or response to IFNβ. In the present case-control study, we evaluated the association between three SNPs at nt -123 (A or C, rs17000900), nt -88 (G or T, rs2071430), and nt +20 (A or C, rs464138) and MS risk as well as treatment response in a population of Iranian MS patients including 146 IFNβ responders and 85 non-responders as well as 180 healthy controls. The AGA (-123, -88, +20) haplotype was more frequent in controls compared with MS cases (P = 0.038, OR (95% CI) = 1.77 (1.03-3.02)). Of particular note, the frequency of rs464138 AA genotype was significantly higher in responders compared with non-responders. However, the allele and genotype frequencies of other SNPs were not significantly different among patient subtypes or between patients and controls. Besides, we have demonstrated that CGC, ATA, and AGA (-123, -88, +20) haplotypes were significantly associated with IFNβ response in MS patients. As SNPs on MxA promoter region might participate in MS patients' response to IFNβ, prior patients genotyping may increase the rate of responsiveness and help in individualized selection of treatment options.
Insights
Genetic variations in the Myxovirus resistance protein A (MxA) gene may influence multiple sclerosis (MS) risk and response to interferon-beta (IFNβ) therapy. Specific MxA haplotypes are linked to treatment outcomes in MS patients.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Pharmacogenetics
Background:
- Multiple sclerosis (MS) is a complex autoimmune disorder affecting the central nervous system.
- Genetic and environmental factors influence MS pathogenesis and response to therapies like interferon-beta (IFNβ).
- Myxovirus resistance protein A (MxA) is an IFNβ-induced gene implicated in MS.
Purpose of the Study:
- To investigate the association between single nucleotide polymorphisms (SNPs) in the MxA gene and MS risk.
- To evaluate the relationship between MxA SNPs and response to IFNβ treatment in Iranian MS patients.
- To identify potential genetic markers for predicting IFNβ treatment efficacy in MS.
Main Methods:
- A case-control study involving 146 IFNβ-responding MS patients, 85 non-responding MS patients, and 180 healthy controls.
- Genotyping of three MxA promoter SNPs: rs17000900 (nt -123), rs2071430 (nt -88), and rs464138 (nt +20).
- Analysis of SNP and haplotype frequencies to assess associations with MS risk and IFNβ response.
Main Results:
- The AGA (-123, -88, +20) haplotype was more frequent in healthy controls than in MS cases.
- The rs464138 AA genotype was significantly more prevalent in IFNβ responders compared to non-responders.
- CGC, ATA, and AGA haplotypes showed significant associations with IFNβ response in MS patients.
Conclusions:
- Specific MxA promoter SNPs and haplotypes are associated with IFNβ treatment response in multiple sclerosis patients.
- MxA gene variations may play a role in determining individual responses to IFNβ therapy.
- Genotyping MxA SNPs could aid in personalized treatment selection for MS patients, potentially improving therapeutic outcomes.