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Inverse Relation between MxA Gene Expression and Age in Multiple Sclerosis Patients Reveals a Gender Difference in
Mohammad Taheri1, Mohammadreza Mirinezhad2, Mir Davood Omrani1
1Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease of the central nervous system that women are at a higher risk to acquire than men. Myxovirus resistance protein A (MxA) is used as a predictive marker of bioactivity of interferon-beta (IFN-β) therapy in MS patients. This study was undertaken in west of Iran to investigate gender differences in the expression level of MxA in relapsing-remitting MS (RRMS) patients receiving IFN-β therapy, compared with untreated normal individuals. The expression level of the MxA gene in RRMS samples were compared to untreated normal individuals using the extracted RNA from whole blood of 50 RRMS patients (31 females and 19 males) and 50 normal controls (29 females and 21 males). All patients were HLA-DRB1*15 negative and responded to IFN-β with a normal vitamin D level. The level of MxA gene expression was measured by quantitative RT-PCR. The levels of gene expression were decreased in RRMS patients compared with normal counterparts (p=0.025). This decrease was significant in females (p=0.009) compared to males (p>0.05). The level of expression varied across different female age-groups with no significant difference in women younger than 30 years, but a significant decrease in expression in women between 30 to 40 years or above 40 years of age was seen. There was neither linear correlation between the MxA expression level and risk of expanded disability status scale of Kurtzke (EDSS); nor were there any significant correlation between expression status of MxA and duration of the disease. In conclusion, the decrease in the level of MxA expression in MS patients treated with IFN-β when compared to normal individuals was significantly lower in females than males. This demonstrated a gender bias in the response to IFN-β therapy that will need to be confirmed and further investigated in more detail.
Insights
This study found lower Myxovirus resistance protein A (MxA) gene expression in multiple sclerosis (MS) patients treated with interferon-beta (IFN-β). This decrease was more pronounced in females, suggesting a gender bias in IFN-β therapy response.
Area of Science:
- Neuroimmunology
- Genetics
- Pharmacogenomics
Background:
- Multiple sclerosis (MS) is an inflammatory central nervous system disease with higher prevalence in women.
- Myxovirus resistance protein A (MxA) serves as a biomarker for interferon-beta (IFN-β) treatment efficacy in MS.
- Investigating gender-specific responses to IFN-β therapy is crucial for personalized treatment strategies.
Purpose of the Study:
- To examine gender differences in MxA gene expression levels in relapsing-remitting MS (RRMS) patients undergoing IFN-β therapy.
- To compare MxA expression in RRMS patients with healthy controls.
- To explore correlations between MxA expression, age, disease duration, and disability in MS patients.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure MxA gene expression.
- Whole blood samples were collected from 50 RRMS patients (31 female, 19 male) and 50 healthy controls (29 female, 21 male).
- Patient cohorts were characterized by HLA-DRB1*15 negativity, normal vitamin D levels, and response to IFN-β therapy.
Main Results:
- RRMS patients exhibited significantly decreased MxA gene expression compared to normal individuals (p=0.025).
- This reduction was significantly more pronounced in female RRMS patients (p=0.009) than in males (p>0.05).
- MxA expression levels varied by age in females, with significant decreases observed in those aged 30-40 and over 40.
Conclusions:
- A notable decrease in MxA expression was observed in IFN-β-treated MS patients compared to controls, with a significant gender disparity.
- The findings suggest a potential gender bias in the therapeutic response to IFN-β in MS patients.
- Further research is warranted to validate and elucidate the mechanisms behind this observed gender-specific response.