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Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A
Nada Sherif Amin1, Mostafa K Abd El-Aziz1, Mohamed Hamed2
1Clinical Pharmacology and Pharmacogenomics Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
Background:
Multiple sclerosis (MS) is characterized by a complex etiology that is reflected in the lack of consistently predictable treatment responses across patients of seemingly similar characteristics. Approaches to demystify the underlying predictors of aberrant treatment responses have made use of genome-wide association studies (GWAS), with imminent progress made in identifying single nucleotide polymorphisms (SNPs) associated with MS risk, disease progression, and treatment response. Ultimately, such pharmacogenomic studies aim to utilize the approach of personalized medicine to maximize patient benefit and minimize rate of disease progression.
Objective:
Very limited research is available around the long intergenic non-coding RNA (linc)00513, recently being reported as a novel positive regulator of the type-1 interferon (IFN) pathway, following its overexpression in the presence of two polymorphisms: rs205764 and rs547311 in the promoter region of this gene. We attempt to provide data on the prevalence of genetic variations at rs205764 and rs547311 in Egyptian MS patients, and correlate these polymorphisms with the patients' responses to disease-modifying treatments.
Methods:
Genomic DNA from 144 RRMS patients was isolated and analyzed for genotypes at the positions of interest on linc00513 using RT-qPCR. Genotype groups were compared with regards to their response to treatment; additional secondary clinical parameters including the estimated disability status score (EDSS), and onset of the disease were examined in relation to these polymorphisms.
Results:
Polymorphisms at rs205764 were associated with a significantly higher response to fingolimod and a significantly lower response to dimethylfumarate. Moreover, the average EDSS of patients carrying polymorphisms at rs547311 was significantly higher, whereas no correlation appeared to exist with the onset of MS.
Conclusion:
Understanding the complex interplay of factors influencing treatment response is pivotal in MS. One of the factors contributing to a patient's response to treatment, as well as disease disability, may be polymorphisms on non-coding genetic material, such as rs205764 and rs547311 on linc00513. Through this work, we propose that genetic polymorphisms may partially drive disease disability and inconsistent responses to treatment in MS; we also aim to draw attention towards genetic approaches, such as screening for specific polymorphisms, to possibly direct treatment choices in such a complex disease.
Insights
Genetic variations in linc00513, specifically rs205764 and rs547311, impact multiple sclerosis (MS) treatment effectiveness and disease disability. These findings suggest genetic screening may personalize MS treatment strategies.
Area of Science:
- Genetics and Genomics
- Pharmacogenomics
- Neuroimmunology
Background:
- Multiple sclerosis (MS) exhibits variable treatment responses due to complex etiology.
- Genome-wide association studies (GWAS) identify single nucleotide polymorphisms (SNPs) linked to MS risk, progression, and treatment outcomes.
- Pharmacogenomic approaches aim for personalized medicine in MS management.
Purpose of the Study:
- Investigate the prevalence of genetic variations (rs205764 and rs547311) in the linc00513 gene in Egyptian MS patients.
- Correlate these linc00513 polymorphisms with patient responses to disease-modifying treatments.
- Examine the association of these polymorphisms with clinical parameters like disability status and disease onset.
Main Methods:
- Genomic DNA isolation from 144 relapsing-remitting MS (RRMS) patients.
- Genotyping of linc00513 polymorphisms (rs205764 and rs547311) using RT-qPCR.
- Comparison of genotype groups regarding treatment response, EDSS, and disease onset.
Main Results:
- rs205764 polymorphisms were linked to significantly higher response to fingolimod and lower response to dimethylfumarate.
- Patients with rs547311 polymorphisms showed a significantly higher average EDSS.
- No significant correlation was found between these polymorphisms and the onset of MS.
Conclusions:
- Genetic polymorphisms in linc00513 (rs205764, rs547311) may influence MS treatment response and disease disability.
- These findings support the role of non-coding genetic material in MS heterogeneity.
- Genetic screening for specific polymorphisms could aid in directing personalized treatment choices for MS patients.
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