HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
Fabiana Paladini1, Francesca Belfiore, Elisa Cocco
1Department of Cell Biology and Development, University "La Sapienza", via dei Sardi, 70, 00185 Roma, Italy. fabiana.paladini@uniroma1.it
Arthritis Research & Therapy
|November 17, 2009
Summary
This study identifies a significant genetic association between ankylosing spondylitis (AS) and a specific haplotype in the HLA-E to HLA-C region. This finding highlights the role of natural killer cell activity in AS pathogenesis.
Area of Science:
- Immunogenetics
- Human Molecular Genetics
- Rheumatology
Background:
- Ankylosing spondylitis (AS) is a chronic inflammatory disease strongly linked to the HLA-B27 gene.
- Previous research suggests additional human leukocyte antigen (HLA) genetic factors contribute to AS susceptibility.
Purpose of the Study:
- To investigate the presence of an additional HLA susceptibility locus between the HLA-E and HLA-C genes in the Sardinian population.
- To identify specific genetic markers associated with AS in this region.
Main Methods:
- Genotyping of six single nucleotide polymorphisms (SNPs) in the HLA-E to HLA-C region in 200 controls and 120 AS patients.
- Comparison of allele, genotype, and haplotype frequencies between patient and control groups.
Main Results:
- A significant increase in the HLA-E functional polymorphism (rs1264457, allele A) was observed in AS patients.
- The frequency of the AAGA haplotype between HLA-E and HLA-C was significantly higher in AS patients (68%) compared to controls (42%).
- Increased homozygous genotypes for rs1264457 were found in AS patients.
Conclusions:
- A strong association exists between a specific haplotype in the HLA-E to HLA-C region and AS.
- The HLA-E functional polymorphism rs1264457 shows the strongest association with AS.
- These findings suggest that natural killer (NK) cell activity, mediated by HLA-E-NKG2A interactions, may play a role in AS pathogenesis.
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