Promoter polymorphism of IL-10 and severity of multiple sclerosis

Functional polymorphisms of the genes for interleukin-10 (IL-10; promoter position -1082), chemokine receptor-5 (CCR5 32 bp deletion), tumor necrous factor-α (TNFα promoter position -308) and cytotoxic T-lymphocyte antigen-4 (CTLA-4 exon I position 49) were investigated for possible influence on susceptibility and outcome of multiple sclerosis (MS). The polymorphisms were typed by polymerase chain reaction based methods or by direct sequencing in MS patients (n = 93-116) and controls (n = 109 400). The studied genes were not associated with MS susceptibility. Patients were classified as suffering from a mild/moderate [Expanded Disability Status Scale (EDSS) 0 5.5] or severe (EDSS 6-8.0) form of MS. The AG genotype of IL-10 proved to be protective against severe MS in all patients (OR = 0.32, P = 0.010), the effect being increased over the years (10 years; OR = 0.33, P = 0.043, 15 years; OR = 0.21, P = 0.025 or 20 years; OR = 0.14, P = 0.026). Our results suggest that differential production of IL-10 might be a factor in the severity of MS.