HLA-class I markers and multiple sclerosis susceptibility in the Italian population
L Bergamaschi1, M A Leone, M E Fasano
1Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases, University of Eastern Piedmont, Via Solaroli 17, Novara, Italy.
Genes and Immunity
|November 13, 2009
Summary
The human leukocyte antigen A*02 (HLA-A*02) marker offers significant protection against multiple sclerosis (MS). The HLA-Cw*05 marker enhances this protection when present with HLA-A*02, but can increase risk independently.
Area of Science:
- Immunogenetics
- Human Leukocyte Antigen (HLA) complex
- Multiple Sclerosis (MS) pathogenesis
Background:
- Previous research identified associations between specific HLA-class I markers (HLA-A*02, HLA-Cw*05) and MOG-142L with multiple sclerosis (MS).
- The interplay and independent contributions of these markers in MS risk modulation require further investigation.
- Understanding these genetic associations is crucial for elucidating MS etiology.
Purpose of the Study:
- To test the association of HLA-A*02 and HLA-Cw*05 with MS in a large Italian cohort.
- To explore the combined effect of HLA-A*02, HLA-Cw*05, and MOG-142L in modulating MS risk.
- To investigate the independent and interactive roles of these HLA markers in MS susceptibility.
Main Methods:
- Genotyping analysis of HLA-A*02 and HLA-Cw*05 in 1273 Italian MS patients and 1075 matched controls.
- Statistical analysis including odds ratio (OR) and confidence intervals (CI) to assess marker associations.
- Exploration of linkage disequilibrium and multiplicative interactions between the studied HLA markers.
Main Results:
- HLA-A*02 demonstrated a statistically robust protective effect against MS (OR=0.61, P<10(-9)), independent of HLA-DRB1 alleles.
- The previously observed protective effect of MOG-142L was attributed to its linkage disequilibrium with HLA-A*02.
- HLA-Cw*05 enhanced HLA-A*02's protection (OR=0.22 in double positive vs. 0.69 in HLA-A*02 positive/Cw*05 negative), showing significant interaction (P=4.94 x 10(-5)).
- In the absence of HLA-A*02, HLA-Cw*05 acted as a risk factor, particularly with HLA-DRB1*03 (OR=3.89).
Conclusions:
- HLA-A*02 is a significant protective factor for multiple sclerosis in the Italian population.
- HLA-Cw*05 modulates the protective effect of HLA-A*02, suggesting complex genetic interactions in MS.
- HLA-Cw*05 may represent a risk marker in specific genetic contexts, highlighting its dual role in MS susceptibility.
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