Researchers Determine Specific Genetic Associations With Multiple Sclerosis
In a recent meta-analysis published in the International Journal of Molecular Sciences, a team of researchers found evidence regarding the association between specific polymorphisms of the gene CD24 and MS using a method that combined data from case-control studies with family-based data.
Multiple sclerosis (MS) is a chronic and complex demyelinating disease of the central nervous system (CNS) with an occurrence of about 0.1% in Caucasian young adults. The development of MS is attributed mainly to genetic susceptibility combined with environmental factors.
Of particular note, CD24 is a gene that has been investigated thoroughly in regard to its association with autoimmune diseases, including MS, with promising results. Four polymorphisms of the CD24 gene have been found to be implicated in the etiology of MS and various degenerative diseases. These polymorphisms are: (a) a C-to-T substitution at nucleotide 226 resulting in a Ala57Val substitution; (b) a TG dinucleotide deletion at positions 1527–1528; (c) an A-to-G substitution at nucleotide 1056; and (d) an A-to-G substitution at nucleotide 1626.
A mutation is defined as any change in a DNA sequence away from normal. Polymorphism is the characteristic of being able to assign a different meaning or usage to something in different contexts. In contrast with a mutation, a polymorphism is a DNA sequence variation that is common in the population. Polymorphism results from evolutionary processes, as does any aspect of a species. It is heritable and is modified by natural selection.
A number of case-control studies have been performed to investigate the putative association of CD24 gene polymorphisms with MS development and progression, although the results are debatable. In the meta-analysis titled “Polymorphisms of the CD24 Gene Are Associated with Risk of Multiple Sclerosis: A Meta-Analysis,” Pantelis G. Bagos from the Department of Computer Science and Biomedical Informatics, University of Thessaly in Greece, investigated four polymorphisms of the CD24 gene regarding their associations with MS.
A total of 19 articles were retrieved from the literature search from which seven articles with eight studies were found to fulfill the eligibility criteria for the meta-analysis of the CD24 226 C>T polymorphism comprising 2085 patients and 2295 healthy controls.
Results showed that polymorphism 226 C>T (Ala57Val) of the CD24 gene was related with MS. The researchers also found that the = 1527–1528 TG>del polymorphism is negatively related with MS, and that the 1056 A>G and 1626 A>G polymorphisms were not associated with MS.
What This Means for MS Patients
In conclusion, the CD24 226 C>T polymorphism (a polymorphism is when two or more clearly different phenotypes exist in the same population) increases the risk of MS, while the 1527-1528 TG>del polymorphism seems to have a protective role against MS, suggesting that these two polymorphisms can be used as predictive biomarkers for MS development.
If two genes/traits/loci are in linkage equilibrium, it means that they are inherited completely independently in each generation. An example would be loci that are on two different chromosomes and encode unrelated, non-interacting proteins. If two genes are in linkage disequilibrium, it means that certain alleles of each gene are inherited together more often than would be expected by chance. According to the researchers, additional studies investigating linkage disequilibrium, between these CD24 polymorphisms, gene–gene interactions, or even gene-environment interactions would be helpful in better understanding the role of the CD24 gene in MS onset and development.