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TAP2 gene polymorphism contributes to genetic susceptibility to multiple sclerosis
H Moins-Teisserenc1, G Semana, M Alizadeh
1Laboratory for Immunology and Histocompatibility, INSERM Unit 396, Saint Louis Hospital, Paris, France.
Abstract:
MS is an autoimmune demyelinating disease that has been known to be associated with the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype. TAP1 and TAP2, two genes encoded within the MHC class II region between HLA-DP and -DQ loci, display genetic variability and are involved in the transport of antigenic peptides from the cytoplasm to the endoplasmic reticulum. Comparison of 116 MS patients with Caucasoid controls did not reveal any significant correlation between the previously described alleles of the TAP1 and TAP2 genes and MS. We report here an additional TAP2 dimorphism at codon 386, called I and J, corresponding to a silent mutation. An increased frequency of the J variant was observed in the patient population. The J mutation was not found in linkage disequilibrium with the HLA-DRB1*1501 allele and can be considered an additional genetic susceptibility marker of the disease.
Insights
Multiple Sclerosis (MS) susceptibility is linked to a novel TAP2 gene variant (J). This genetic marker, independent of the HLA-DRB1*1501 allele, offers new insights into MS pathogenesis.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Molecular Biology
Background:
- Multiple Sclerosis (MS) is an autoimmune demyelinating disease.
- A known genetic association exists with the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype.
- TAP1 and TAP2 genes, within the MHC class II region, are crucial for antigen presentation.
Purpose of the Study:
- To investigate the association of TAP1 and TAP2 gene variability with MS.
- To identify novel genetic susceptibility markers for MS.
Main Methods:
- Comparison of TAP1 and TAP2 alleles in 116 MS patients and Caucasoid controls.
- Analysis of a newly identified TAP2 dimorphism at codon 386 (I and J variants).
- Assessment of linkage disequilibrium with the HLA-DRB1*1501 allele.
Main Results:
- No significant correlation was found between previously described TAP1/TAP2 alleles and MS.
- An increased frequency of the TAP2 'J' variant was observed in MS patients.
- The TAP2 'J' variant was not in linkage disequilibrium with HLA-DRB1*1501.
Conclusions:
- The TAP2 'J' variant represents a potential independent genetic susceptibility marker for MS.
- This finding contributes to understanding the genetic architecture of MS.
- Further research is warranted to elucidate the functional role of the TAP2 'J' variant in MS.