Association of interleukin-1 β and interleukin-1 receptor antagonist genes with disease severity in MS

Abstract

Objective: To investigate whether polymorphisms in the interleukin (IL)-1β and IL-1 receptor antagonist (IL-1RA) genes are associated with both susceptibility to and clinical characteristics of MS. Background: Genetic susceptibility to MS is determined by many partially identified genes. The genes encoding various cytokines are logical candidates for MS susceptibility and phenotype. Methods: Genotypes were determined from 148 patients with clinically definite MS and 98 healthy controls. All the patients were unrelated, Dutch, and white. Patient files were reviewed for disease type, initial symptoms, age at onset of disease, and rate of disease progression. Results: No significant differences in genotypes, allele frequencies, or carrier frequencies were found between MS patients and healthy controls. Stratification for disease type (relapsing-remitting, primary progressive, or secondary progressive) did not provide significant differences between patients and controls. However, a specific IL-1RA/IL-1β combination was associated with disease severity. MS patients with the IL-1RA allele 2⁺/IL-1β allele 2⁻ combination had a higher rate of progression on the Expanded Disability Status Scale when compared with the other possible combinations (p = 0.007). Conclusions: IL-1RA and IL-1β are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.