Related Experiment Videos
Tumor necrosis factor polymorphism in multiple sclerosis: no additional association independent of HLA
M P Roth1, L Nogueira, H Coppin
1Centre de Recherche sur le Polymorphisme Génétique des Populations Humaines, CNRS UPR 8291, CHU Purpan, Toulouse, France.
Abstract:
In order to investigate whether genes coding for tumor necrosis factors (TNF) contribute to the pathogenesis of multiple sclerosis (MS) and also whether they have a non-random association with the MS associated HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype, 40 MS patients and their parents were characterized at four polymorphic loci in the region of the TNF genes: a NcoI RFLP and three microsatellites. We were able to determine the parental haplotypes and used those which were not transmitted to the proband as controls. Fifty percent of the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotypes carried the TNFc1-n2-a11-b4 allelic combination in both the patient and the control groups. However, there was no association of any of these TNF polymorphisms with MS, independent of that already described for the class II region. This, with the lack of association of DP alleles with MS, effectively marks the boundaries of the MS associated haplotype.
Insights
Tumor necrosis factor (TNF) gene polymorphisms do not independently contribute to multiple sclerosis (MS) pathogenesis. The study found no direct association between TNF gene variations and MS, beyond the known HLA-DRB1*1501 association.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Human Genetics
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
- The HLA-DRB1*1501 allele is a known genetic risk factor for MS.
- Tumor necrosis factors (TNF) are key immune mediators implicated in inflammatory processes.
Purpose of the Study:
- To investigate the potential contribution of tumor necrosis factor (TNF) genes to multiple sclerosis (MS) pathogenesis.
- To determine if TNF gene polymorphisms are non-randomly associated with the MS-associated HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype.
Main Methods:
- Genetic characterization of 40 MS patients and their parents at four polymorphic loci within the TNF gene region.
- Analysis of a NcoI RFLP and three microsatellites in TNF genes.
- Haplotype analysis using parental data and non-transmitted haplotypes as controls.
Main Results:
- The TNFc1-n2-a11-b4 allelic combination was present in 50% of HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotypes in both MS patients and controls.
- No significant association was found between TNF gene polymorphisms and MS, independent of the class II region associations.
- DP alleles also showed no association with MS.
Conclusions:
- TNF gene polymorphisms do not appear to independently contribute to the pathogenesis of multiple sclerosis.
- The study delineates the boundaries of the MS-associated haplotype, excluding TNF gene involvement beyond the established class II associations.