Polymorphic variants in the PVT1 locus affect multiple sclerosis severity

Multiple sclerosis (MS) is a chronic autoimmune disease, in the pathogenesis of which the concurrence of demyelination of central nervous system (CNS) axons and neurodegeneration plays a role and which is accompanied by progressive neurological dysfunction. Long-term monitoring of patients with MS is needed to rate its severity according to existing scales; it is therefore very relevant to search for genomic markers that can predict the rate of disease progression at early stages. The impact of polymorphic variants in the PVT1 locus on MS severity has not been previously studied.

Objective: to analyze the association of the polymorphic variants rs4645948 in the MYC gene and rs2114358 and rs4410871) in the PVT1 genes with MS severity according to the Multiple Sclerosis Severity Scale (MSSS) separately and as part of biallelic combinations, as well as the possible linkage disequilibrium of the studied single nucleotide polymorphisms for establishing the independence of the observed associations.

Patients and methods. The investigation enrolled 468 Russian MS patients who did not take immunomodulating drugs before blood testing. The patients were divided into two groups: 1) relatively mild MS (MSSS ≤3.5) and 2) relatively severe MS (MSSS >3.5). The polymorphic variants in the PVT1 locus were genotyped by a real-time polymerase chain reaction assay.

Results and discussion. In the MS study group, the carriage of the allele of PVT1 (rs2114358)*G turned out to be associated with the severe course of the disease (pf=0.042; odds ratio (OR)=1.41). The significance of the association increases in the simultaneous carriage of this allele with another variant of the same gene – PVT1 (rs4410871)*T (pf=0.024; OR=1.58). There was no linkage disequilibrium between the components of the biallelic combination.

Conclusion. The polymorphic variants in the PVT1 locus are associated with the severity of MS.

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