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

Objective: To investigate whether polymorphisms in the interleukin (IL)-1 b eta and IL-1 receptor antagonist (IL-1RA) genes are associated with both su sceptibility to and clinical characteristics of MS. Background: Genetic sus ceptibility to MS is determined by many partially identified genes. The gen es encoding various cytokines are logical candidates far MS susceptibility and phenotype. Methods: Genotypes were determined from 148 patients with cl inically definite MS and 98 healthy controls. All the patients were unrelat ed, Dutch, and white. Patient files were reviewed for disease type, initial symptoms, age at onset of disease, and rate of disease progression. Result s: No significant differences in genotypes, allele frequencies, or carrier frequencies were found between MS patients and healthy controls. Stratifica tion for disease type (relapsing-remitting, primacy progressive, or seconda ry progressive) did not provide significant differences between patients an d controls. However, a specific IL-1RA/IL-1 beta combination was associated with disease severity. MS patients with the IL-1RA allele 2(+)/IL-1 beta a llele 2(-) combination had a higher rate of progression on the Expanded Dis ability Status Scale when compared with the other possible combinations (p = 0.007). Conclusions: IL-1RA and IL-1 beta are disease severity genes rath er than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.