Relapse rates were age- and time-dependent. Our observations have clinical implications: 1) any drug able to modify relapse rates has the greatest potential for a population impact in patients <40 years old and within the first few demi-decades of disease; 2) continuation of drug beyond these times may be of limited value; 3) long-term follow-up studies must consider that relapse rates probably decline at different rates over time according to the patient's onset age; 4) a relapse-quiescent period in MS is not uncommon.
The contribution of genetic factors to the age at onset in multiple sclerosis is poorly understood. Our objective was to investigate the disease modifying effects of HLA-DRB1 alleles and allele interactions on age at onset of multiple sclerosis. High-resolution four-digit HLA-DRB1 genotyping was performed in a cohort of 461 multiple sclerosis patients from the Perth Demyelinating Diseases Database. Carriage of the HLA-DRB1*1501 risk allele was not significantly associated with age at onset but HLA-DRB1*0801 was associated with a later onset of the disease. The HLA-DRB1*0401 allele was associated with a reduced age at onset when combined with DRB1*1501 but may delay age at onset when combined with DRB1*0801. These findings indicate that epistatic interactions at the HLA-DRB1 locus have significant modifying effects on age at onset of multiple sclerosis and demonstrate the value of high-resolution genotyping in detecting such associations.
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