influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis.

Background: Whether genetic factors influence the long-term course of multiple sclerosis (MS) is unresolved.

Objective: To determine the influence of on long-term disease course in a homogeneous cohort of clinically isolated syndrome (CIS) patients.

Methods: One hundred seven patients underwent clinical and MRI assessment at the time of CIS and after 1, 3, 5 and 15 years. status was determined using Sanger sequencing and tagging of the rs3135388 polymorphism. Linear/Poisson mixed-effects models were used to investigate rates of change in EDSS and MRI measures based on status.

Results: -positive ( = 52) patients showed a faster rate of disability worsening compared with the -negative ( = 55) patients (annualised change in EDSS 0.14/year vs. 0.08/year,  < 0.025), and a greater annualised change in T2 lesion volume (adjusted difference 0.45 mL/year,  < 0.025), a higher number of gadolinium-enhancing lesions, and a faster rate of brain (adjusted difference -0.12%/year,  < 0.05) and spinal cord atrophy (adjusted difference -0.22 mm/year,  < 0.05).

Interpretation: These findings provide evidence that the allele plays a role in MS severity, as measured by long-term disability worsening and a greater extent of inflammatory disease activity and tissue loss. may provide useful information when considering prognosis and treatment decisions in early relapse-onset MS.