Exploring the Role of SIRT1 Gene Polymorphisms and Serum Levels in Multiple Sclerosis

Multiple sclerosis (MS) is a complex immune-mediated neurodenerative disease characterized by demyelination and neuroaxonal damage in the central nervous system (CNS). The etiology of MS involves both genetic and environmental factors. Studies have shown that individuals with a family history of MS are at higher risk, and certain genetic variations associated with immune function can increase susceptibility to MS. Among these genetic factors, SIRT1, a member of the sirtuin family, has been of particular interest due to its role in regulating cellular processes such as energy metabolism, DNA repair, aging, and inflammation.

The study, "Role of SIRT1 Gene Polymorphisms and Serum Levels in Patients with Multiple Sclerosis," aimed to investigate the prevalence of specific SIRT1 gene polymorphisms (rs3818292, rs3758391, and rs7895833) and serum levels in MS patients within the Lithuanian population.

A total of 500 participants were enrolled in the study, comprising 250 MS patients and 250 healthy controls. Genotyping of the selected SIRT1 polymorphisms was conducted using the RT-PCR method, while serum SIRT1 levels were measured using the ELISA method. Statistical analysis was performed using IBM SPSS version 29.0.

Findings
The study revealed significant associations between SIRT1 polymorphisms and MS:

SIRT1 rs3818292:
Associated with increased odds of developing MS under dominant and allelic models.
The AG genotype was more prevalent in MS patients compared to controls.

SIRT1 rs3758391:
Showed strong associations with MS across various genetic models.
The CT genotype was notably more common in the MS group.

SIRT1 rs7895833:
Linked to a higher risk of MS under multiple genetic models.
The AG genotype was significantly more frequent among MS patients.

Furthermore, sex-specific analyses indicated that these polymorphisms had a more pronounced effect in females. Age-specific analyses suggested distinct associations, with rs3758391 and rs7895833 linked to increased MS risk in younger patients, while rs3818292 and rs7895833 were associated with older patients.

Serum SIRT1 Levels
Serum SIRT1 levels were significantly lower in MS patients compared to controls, supporting the hypothesis that decreased SIRT1 expression is related to increased autoimmunity and neurodegeneration. Specifically, rs3818292 AA, rs3758391 CT, and rs7895833 AA and AG carriers in the control group had higher SIRT1 levels than those in the MS group.

Conclusion
Genetic variations in SIRT1 rs3818292, rs3758391, and rs7895833 are associated with an increased risk of developing MS, with notable differences in gender and age. Lower serum SIRT1 levels in MS patients further underline the gene's potential as a biomarker and therapeutic target in MS management.

This comprehensive study underscores the complex interplay between genetics and disease, paving the way for future research into targeted therapies that could mitigate the impact of genetic predispositions on MS progression.

References:
Kaikaryte, K., Gedvilaite, G., Balnyte, R., Uloziene, I., & Liutkeviciene, R. (2023). Role of SIRT1 Gene Polymorphisms and Serum Levels in Patients with Multiple Sclerosis. Diagnostics, 13(3287).