Multiple sclerosis (MS) is a neurodegenerative disease with various factors affecting its etiology.Overproduction of nitric oxide and subsequent lesions of biopolymers are some of the possible causes of the disease. This study aimed to measure the most relevant nitrosative and oxidative stress biomarkers and the level of modi ed DNA bases in patients with MS. Each parameter was assayed in 25 patients with MS and 25 healthy controls. This study involved detecting blood plasma and serum nitric oxide metabolites by chemiluminescence detector Sievers NOA-280i, malondialdehyde (MDA) measurements with thiobarbituric acid reactive substance (TBARS) assay, detection of oxidized purines and pyrimidines with the enzyme-modi ed comet assay. Statistical analysis of the results was performed by one-way analysis of variance (ANOVA) and unpaired t test for the comparison of less than three data sets. DNA single-strand breaks, levels of modi ed purines and pyrimidines, as well as nitrite and nitrate levels in plasma and serum samples, were signi cantly higher in patients with MS than in healthy controls. On the contrary, MDA levels appeared to be lower in patients with MS.
Several polymorphisms in genes related to the ubiquitin-proteasome system exhibit an association with pathogenesis and prognosis of various human autoimmune diseases. Our previous study reported the association between multiple sclerosis (MS) and the
PSMA3
-rs2348071 polymorphism in the Latvian population. The current study aimed to evaluate the
PSMA6
and
PSMC6
genetic variations, their interaction between each other and with the rs2348071, on the susceptibility to MS risk and response to therapy in the Latvian population.
PSMA6
-rs2277460, -rs1048990 and
PSMC6
-rs2295826, -rs2295827 were genotyped in the MS case/control study and analysed in terms of genotype-protein correlation network. The possible association with the disease and alleles, single- and multi-locus genotypes and haplotypes of the studied loci was assessed. Response to therapy was evaluated in terms of ‘no evidence of disease activity’. To the best of our knowledge, the present study was the first to report that single- and multi-loci variations in the
PSMA6, PSMC6
and
PSMA3
proteasome genes may have contributed to the risk of MS in the Latvian population. The results of the current study suggested a potential for the
PSMA6
-rs1048990 to be an independent marker for the prognosis of interferon-β therapy response. The genotype-phenotype network presented in the current study provided a new insight into the pathogenesis of MS and perspectives for future pharmaceutical interventions.
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