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HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia

INTRODUCTION: Ankylosing spondylitis (AS) is a severe, chronic inflammatory disease strongly associated with HLA-B27. The presence of additional HLA risk factors has been suggested by several studies. The aim of the current study is to assess the occurrence of an additional HLA susceptibility locus...

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Autores principales: Paladini, Fabiana, Belfiore, Francesca, Cocco, Elisa, Carcassi, Carlo, Cauli, Alberto, Vacca, Alessandra, Fiorillo, Maria Teresa, Mathieu, Alessandro, Cascino, Isabella, Sorrentino, Rosa
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003531/
https://www.ncbi.nlm.nih.gov/pubmed/19912639
http://dx.doi.org/10.1186/ar2860
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author Paladini, Fabiana
Belfiore, Francesca
Cocco, Elisa
Carcassi, Carlo
Cauli, Alberto
Vacca, Alessandra
Fiorillo, Maria Teresa
Mathieu, Alessandro
Cascino, Isabella
Sorrentino, Rosa
author_facet Paladini, Fabiana
Belfiore, Francesca
Cocco, Elisa
Carcassi, Carlo
Cauli, Alberto
Vacca, Alessandra
Fiorillo, Maria Teresa
Mathieu, Alessandro
Cascino, Isabella
Sorrentino, Rosa
author_sort Paladini, Fabiana
collection PubMed
description INTRODUCTION: Ankylosing spondylitis (AS) is a severe, chronic inflammatory disease strongly associated with HLA-B27. The presence of additional HLA risk factors has been suggested by several studies. The aim of the current study is to assess the occurrence of an additional HLA susceptibility locus in the region between HLA-E and HLA-C in the Sardinian population. METHODS: 200 random controls, 120 patients with AS and 175 HLA-B27 positive controls were genotyped for six single nucleotide polymorphisms (SNPs) spanning the HLA region between HLA-E and HLA-C loci previously shown to harbour an additional susceptibility locus for AS. Allele, genotype and haplotype frequencies were compared. RESULTS: The data confirm our previous finding of a significant increase in patients with AS of allele A at SNP rs1264457 encoding for an Arg at the functional HLA-E polymorphism (Arg(128)/Gly(128)). This was due to a remarkable increase in the frequency of genotype A/A in patients vs HLA-B27-matched controls (51% vs 29%; P for trend: 5 × 10(-5)). Genotype distribution of three other SNPs mapping in genes (GNL1, PRR3 and ABCF-1) close to HLA-E and showing high LD with it, was also significantly skewed. Accordingly, haplotype distribution was also remarkably different. The frequency of the haplotype AAGA, is 42% in random controls, increases to 53% in the HLA-B27-positive controls, and reaches 68% in patients with AS (P values: 2 × 10(-11 )vs random and 3 × 10(-4 )vs HLA-B27 controls). CONCLUSIONS: There is a strong association between the presence of a haplotype in genes mapping between HLA-E and HLA-C and AS due to an increase of homozygous markers in patients. The strongest association however, is with the HLA-E functional polymorphism rs1264457. Since HLA-E is the ligand for the NKG2A receptor, these data point to the natural killer (NK) activity as possible player in the pathogenesis of AS.
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spelling pubmed-30035312010-12-18 HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia Paladini, Fabiana Belfiore, Francesca Cocco, Elisa Carcassi, Carlo Cauli, Alberto Vacca, Alessandra Fiorillo, Maria Teresa Mathieu, Alessandro Cascino, Isabella Sorrentino, Rosa Arthritis Res Ther Research Article INTRODUCTION: Ankylosing spondylitis (AS) is a severe, chronic inflammatory disease strongly associated with HLA-B27. The presence of additional HLA risk factors has been suggested by several studies. The aim of the current study is to assess the occurrence of an additional HLA susceptibility locus in the region between HLA-E and HLA-C in the Sardinian population. METHODS: 200 random controls, 120 patients with AS and 175 HLA-B27 positive controls were genotyped for six single nucleotide polymorphisms (SNPs) spanning the HLA region between HLA-E and HLA-C loci previously shown to harbour an additional susceptibility locus for AS. Allele, genotype and haplotype frequencies were compared. RESULTS: The data confirm our previous finding of a significant increase in patients with AS of allele A at SNP rs1264457 encoding for an Arg at the functional HLA-E polymorphism (Arg(128)/Gly(128)). This was due to a remarkable increase in the frequency of genotype A/A in patients vs HLA-B27-matched controls (51% vs 29%; P for trend: 5 × 10(-5)). Genotype distribution of three other SNPs mapping in genes (GNL1, PRR3 and ABCF-1) close to HLA-E and showing high LD with it, was also significantly skewed. Accordingly, haplotype distribution was also remarkably different. The frequency of the haplotype AAGA, is 42% in random controls, increases to 53% in the HLA-B27-positive controls, and reaches 68% in patients with AS (P values: 2 × 10(-11 )vs random and 3 × 10(-4 )vs HLA-B27 controls). CONCLUSIONS: There is a strong association between the presence of a haplotype in genes mapping between HLA-E and HLA-C and AS due to an increase of homozygous markers in patients. The strongest association however, is with the HLA-E functional polymorphism rs1264457. Since HLA-E is the ligand for the NKG2A receptor, these data point to the natural killer (NK) activity as possible player in the pathogenesis of AS. BioMed Central 2009 2009-11-13 /pmc/articles/PMC3003531/ /pubmed/19912639 http://dx.doi.org/10.1186/ar2860 Text en Copyright ©2009 Paladini et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Paladini, Fabiana
Belfiore, Francesca
Cocco, Elisa
Carcassi, Carlo
Cauli, Alberto
Vacca, Alessandra
Fiorillo, Maria Teresa
Mathieu, Alessandro
Cascino, Isabella
Sorrentino, Rosa
HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
title HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
title_full HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
title_fullStr HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
title_full_unstemmed HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
title_short HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
title_sort hla-e gene polymorphism associates with ankylosing spondylitis in sardinia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003531/
https://www.ncbi.nlm.nih.gov/pubmed/19912639
http://dx.doi.org/10.1186/ar2860
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