Genetic differences between primary progressive and relapsing-remitting multiple sclerosis: The impact of immune-related genes variability.

BACKGROUND:Multiple sclerosis (MS) is a chronic autoimmune disease of CNS with a highly heterogeneous clinical course. The role of the genetic variability in determination of MS course is not yet well established. We aimed to estimate the impact of immune-related genes variability in the genetic architecture of two clinically different MS courses - primary progressive (PPMS) and relapsing-remitting (RRMS). METHODS:We performed the association analysis of 31 immune-related genes' variants in pairwise comparisons of 110 PPMS patients, 564 RRMS patients and 424 healthy individuals (HI). RESULTS:HLA-DRB1*11 and *15, IL7RA rs6897932*C/C, CXCR5 rs523604*A/A, and CLEC16A rs6498169*G/G were found as MS-associated variants common for PPMS and RRMS. HLA-DRB1*07, IL4 rs2243250*C/C, IRF5 rs4728142*A/A, and IFNAR2 rs2248202*C were PPMS- associated when compared to HI and RRMS, while HLA-DRB1*09 and IL6 rs1800795*C were RRMS-associated when compared to HI and PPMS. In multiple logistic regression and ROC curve analyses composite regression models were characterized by area under the curve values of 0.769, 0.726, and 0.679 in comparisons "PPMS vs HI", "RRMS vs HI", and "PPMS vs RRMS", respectively. CONCLUSION:We revealed genetic variants associated with PPMS, among which both variants common for two MS courses and distinguishing PPMS and RRMS were found. Observed genetic features of two MS courses may underlie different impact of autoimmune inflammatory processes in development of PPMS and RRMS, however additional studies on larger PPMS samples are strictly needed.