Exploring the Impact of VDR Gene Polymorphism (rs1544410) on Multiple Sclerosis Progression
Multiple Sclerosis (MS) is a chronic, potentially debilitating disease affecting the central nervous system, where immunological factors and genetic predispositions play critical roles. Recent studies have hinted at the involvement of Vitamin D in modulating immune responses, suggesting a significant connection between Vitamin D receptor (VDR) gene polymorphisms and MS progression.
The Vitamin D receptor (VDR) is ubiquitously expressed across various immune cells, hinting at its potential role in immunoregulation. Polymorphisms in the VDR gene, such as rs1544410, have been studied with respect to numerous autoimmune conditions, including MS, albeit with varying conclusions regarding their impact on disease susceptibility and progression.
A cross-sectional study was conducted at Charles Nicolle Hospital in Tunisia, focusing on patients diagnosed with relapsing-remitting MS, adhering to the McDonald 2017 criteria. The study aimed to elucidate the influence of the rs1544410 polymorphism on MS progression, categorized through the Multiple Sclerosis Severity Scale (MSSS).
Patients were classified into two groups based on MSSS scores:
Group A (Slow Progressors): MSSS ≤ 5
Group B (Fast Progressors): MSSS > 5
The study examined the rs1544410 polymorphism for all participants, comparing demographic, clinical, and radiological data between the two groups. The association between VDR polymorphism genotypes/alleles and MS progression was analyzed using various statistical methods.
The study encompassed 80 patients, revealing no significant differences in disease progression between different genotypes of the rs1544410 polymorphism. However, certain trends were noted:
Patients with the CC genotype and wild-type allele displayed a more aggressive disease course, characterized by higher EDSS at onset, more relapses within the first year, and rapid progression to secondary stages.
The findings suggest subtle genotype-phenotype correlations, indicating that while the rs1544410 polymorphism alone may not determine MS progression conclusively, it could contribute to understanding the broader genetic context influencing MS pathophysiology. The presence of the CC genotype correlated with more severe disease manifestations, although these observations warrant further investigation in larger, more diverse cohorts.
The study's primary limitation was its small sample size and the homogeneity of the patient population, which may not provide a comprehensive view of the polymorphism's effects across different ethnicities or genetic backgrounds.
This study underscores the complex interplay between genetics and disease progression in MS, particularly the role of Vitamin D and its receptor. While the rs1544410 polymorphism by itself does not conclusively predict MS progression, it contributes to a genetic profile that may predispose individuals to more aggressive forms of the disease. Further research is essential to validate these findings and potentially integrate them into personalized treatment approaches for MS.
Reference:
Jamoussi, M., Alaya, F., Jamoussi, H., Baraket, G., Achouri, A., Mahmoud, M. B., ... & Fredj, M. (2024). Vitamin D receptor gene BsmI (rs1544410) polymorphism: role in multiple sclerosis and genotype-phenotype correlations. Molecular Biology Reports, 51(1), 478.
