Genetic variations in the and proteasome genes are associated with multiple sclerosis and response to interferon-β therapy in Latvians.

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 -rs2348071 polymorphism in the Latvian population. The current study aimed to evaluate the and 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. -rs2277460, -rs1048990 and -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 and 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 -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.