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Association of interleukin-1beta and interleukin-1 receptor antagonist genes with disease severity in MS
H M Schrijver1, J B Crusius, B M Uitdehaag
1Department of Neurology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Objective:
To investigate whether polymorphisms in the interleukin (IL)-1beta 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-1beta combination was associated with disease severity. MS patients with the IL-1RA allele 2+/IL-1beta 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-1beta are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.
Insights
Genetic variations in interleukin-1 receptor antagonist (IL-1RA) and IL-1beta genes do not influence multiple sclerosis (MS) susceptibility. However, specific IL-1RA/IL-1beta gene combinations are linked to increased MS disease severity and faster progression.
Area of Science:
- Neuroimmunology
- Genetics of Autoimmune Diseases
- Cytokine Gene Polymorphisms
Background:
- Genetic factors play a role in multiple sclerosis (MS) susceptibility.
- Cytokine genes are potential candidates for MS susceptibility and phenotype.
- Interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1RA) are key inflammatory mediators.
Purpose of the Study:
- To investigate the association between IL-1beta and IL-1RA gene polymorphisms and MS susceptibility.
- To determine if these polymorphisms correlate with clinical characteristics of MS, including disease severity and progression.
Main Methods:
- Genotyping was performed on 148 Dutch MS patients and 98 healthy controls.
- Patient data on disease type, onset, and progression were analyzed.
- Allele and genotype frequencies were compared between patient and control groups.
Main Results:
- No significant differences in IL-1beta or IL-1RA gene polymorphisms were found between MS patients and controls.
- A specific combination of IL-1RA allele 2 and IL-1beta allele 2 was associated with a higher rate of disability progression in MS patients (p = 0.007).
- Stratification by MS disease type did not reveal significant associations.
Conclusions:
- IL-1RA and IL-1beta gene polymorphisms act as disease severity modifiers, not susceptibility factors, in MS.
- These specific gene polymorphisms may identify MS patient subgroups with a poorer prognosis.
- Further research into cytokine gene variants could refine MS prognostication.