Exploring the Role of Vitamin D-Related Gene Polymorphisms in Multiple Sclerosis Susceptibility: A Study in the Turkish Population

Multiple sclerosis (MS) is a complex and debilitating autoimmune disorder, primarily affecting the central nervous system (CNS) and leading to varying degrees of physical disability. The pathogenesis of MS is not fully understood; however, genetic and environmental factors such as vitamin D levels have been implicated in its development. In this context, the study conducted by Giray Bulut explores the association between genetic polymorphisms in vitamin D metabolizing genes and the vitamin D receptor (VDR) with MS risk in the Turkish population. This research contributes to understanding the genetic underpinnings of MS and the potential role of vitamin D in modulating disease risk.

The study included 187 MS patients and 140 healthy controls, all of Caucasian descent from Central Anatolia, Turkey. Polymorphisms in genes responsible for vitamin D metabolism (CYP24A1, CYP27A1, CYP27B1) and the VDR gene were investigated using Restriction Fragment Length Polymorphism (RFLP) analysis. The study was conducted under ethical standards and with all participants providing informed consent.

Significant findings emerged from the analysis of various polymorphisms:

For the VDR gene polymorphism TaqI (rs731236), the presence of the "G" allele showed a borderline significant reduction in MS risk, suggesting a protective role.
The CYP24A1 gene polymorphism (rs1570669) displayed a strong association with increased MS susceptibility, especially noticeable in the female subgroup, where the risk was further elevated.
For other analyzed polymorphisms in the VDR-ApaI (rs7975232), CYP27A1 (rs6709815), and CYP27B1 (rs4646536), no significant associations were found with MS risk.

The findings highlight the complexity of MS pathogenesis and the potential influence of vitamin D-related genetic variations. The association of the CYP24A1 polymorphism with an increased risk of MS could reflect a disruption in vitamin D metabolism, influencing immune function and disease progression. Conversely, the protective association observed with the VDR gene polymorphism TaqI points towards the beneficial effects of vitamin D in CNS health and immune regulation.

This study underscores the significance of genetic factors in MS and supports the hypothesis that vitamin D's metabolic pathway might influence MS susceptibility. While some polymorphisms show a strong association with the disease, others do not, suggesting that the genetic risk of MS is multifactorial and potentially influenced by other genetic or environmental factors. Future research should aim to replicate these findings in larger cohorts and explore the mechanisms by which these polymorphisms affect vitamin D metabolism and MS pathogenesis.

Reference:
Bulut, G. (2023). ASSOCIATION OF THE VITAMIN D METABOLIZING CYP24A1, CYP27A1, CYP27B1 AND VITAMIN D RECEPTOR GENETIC POLYMORPHISMS WITH MULTIPLE SCLEROSIS RISK IN TURKISH POPULATION.