ALCAM--novel multiple sclerosis locus interfering with HLA-DRB1*1501.
Marta Wagner1, Andrzej Wiśniewski, Małgorzata Bilińska
1Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. marta_wagner@o2.pl
Journal of Neuroimmunology
|March 20, 2013
Summary
The Activated Leukocyte Cell Adhesion Molecule (ALCAM) gene rs6437585 polymorphism increases multiple sclerosis (MS) risk and lowers age of onset. Other ALCAM variants may offer protection in specific genetic contexts.
Area of Science:
- Neuroimmunology
- Genetics
Background:
- Activated Leukocyte Cell Adhesion Molecule (ALCAM) plays a role in leukocyte migration across the blood-brain barrier, a critical process in multiple sclerosis (MS) pathogenesis.
- Genetic variations in ALCAM may influence susceptibility and progression of MS.
Purpose of the Study:
- To investigate the association between ALCAM gene polymorphisms and the risk, progression, and age of onset of MS.
- To explore the potential interaction between ALCAM polymorphisms and the HLA-DRB1*1501 risk allele in MS.
Main Methods:
- Case-control study analyzing ALCAM polymorphisms (rs6437585, rs11559013, rs34926152) in relation to MS.
- Logistic regression analysis was used to assess risk, age of onset, and gene-gene interactions, including with HLA-DRB1*1501.
Main Results:
- The ALCAM rs6437585CT genotype was associated with an increased risk of MS (OR=2.34) and an earlier age of onset (by over 2 years).
- ALCAM polymorphisms rs11559013 and rs34926152 were not directly associated with MS risk but modified the effect of the HLA-DRB1*1501 risk allele.
- Individuals with rs11559013GA/HLA-DRB1*1501+ or rs34926152GT/HLA-DRB1*1501+ genotypes showed a five-fold reduced risk of MS, suggesting a protective effect in HLA-DRB1*1501 positive individuals.
Conclusions:
- The ALCAM rs6437585 polymorphism is a significant genetic risk factor for MS, influencing both disease susceptibility and age of onset.
- Specific ALCAM genotypes (rs11559013GA and rs34926152GT) may confer a protective effect against MS in the context of the HLA-DRB1*1501 risk allele, highlighting complex gene interactions in MS pathogenesis.
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