Exploring the Genetic Landscape of Multiple Sclerosis in Jordan: A Closer Look at SNPs and Clinical Phenotypes

Multiple Sclerosis (MS) impacts approximately 2.5 million individuals globally, manifesting in diverse clinical symptoms that significantly impair mental, physical, and psychological functions. The complexity of MS is underscored by its idiopathic nature, where both genetic and environmental factors play crucial roles in its pathogenesis. Previous studies have identified over 200 MS-associated genetic variants; however, their links to specific clinical phenotypes remain poorly understood, particularly in Middle Eastern populations.

This study aims to identify the correlation between 21 SNPs within the IL7R, LAG3, and CD40 genes and various MS clinical characteristics in a Jordanian cohort. By understanding these associations, the research seeks to contribute to the personalized medical treatment of MS, emphasizing the importance of genetic factors in clinical presentations.

The study included 218 Arab Jordanian MS patients from multiple medical centers across Jordan. Clinical data and blood samples were collected, and vitamin D levels were measured. Genomic DNA was extracted and the SNPs were genotyped using the Sequenom MassARRAY® system. Statistical analyses, including Chi-square, Fisher exact test, and one-way ANOVA, were employed to explore the associations between SNPs and MS phenotypes.

The study found significant associations between multiple SNPs and MS clinical features:

Vitamin D deficiency correlated significantly with three SNPs in the IL7R gene and two in the CD40 gene.
Certain SNPs in the IL7R gene were linked to the number of relapses before treatment and the Expanded Disability Status Scale (EDSS) scores.
One SNP in the LAG3 gene was associated with comorbidity, indicating potential links between this gene and broader immune system regulation.

The findings suggest that specific genetic variants in the IL7R, LAG3, and CD40 genes are associated with distinct clinical outcomes of MS, including disability progression, relapse rate, and comorbidities. These associations could help tailor treatment strategies to individual genetic profiles, improving prognosis and treatment efficacy. The role of vitamin D in modulating MS risk and progression also highlights the need for further research into environmental and nutritional factors in MS management.

This genotype-phenotype correlation study enriches our understanding of the genetic landscape of MS in a Jordanian population, pointing towards a more nuanced approach to treatment that considers genetic predispositions. Future research should expand on these findings with larger cohorts and explore the interaction between genetic and environmental factors in MS pathogenesis.

Reference:
Al-Eitan, L., Al Qudah, M., & Al Qawasmeh, M. (2020). Association of multiple sclerosis phenotypes with single nucleotide polymorphisms of IL7R, LAG3, and CD40 genes in a Jordanian population: A genotype-phenotype study. Biomolecules, 10(3), 356.