Fine mapping of a major histocompatibility complex in ankylosing spondylitis: association of the HLA-DPA1 and HLA-DPB1 regions.
Arthritis Rheum
; 63(11): 3305-12, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21769851
ABSTRACT
OBJECTIVE:
To investigate the potential association of major histocompatibility complex (MHC) markers other than HLA-B27 with ankylosing spondylitis (AS).METHODS:
A total of 603 patients with AS and 542 healthy control subjects, all of whom were HLA-B27 positive, were selected for this study based on clinical criteria. First, high-density genotyping across the MHC region (2,360 single-nucleotide polymorphisms [SNPs]) was performed in a cohort of 191 patients and 241 control subjects. After a fine-mapping study, 5 SNPs from the HLA-DPA1/DPB1 region were validated in a second cohort of 412 patients with AS and 301 healthy control subjects.RESULTS:
Seventeen SNPs located within or near the HLA-DPA1 and HLA-DPB1 loci showed association with AS (P = 1.38 × 10â»5 to 0.05). In addition, multimarker tests, both linkage disequilibrium and sliding windows, showed association of some groups of adjacent SNPs within the HLA-DPA1/DPB1 region with AS (P = 1.0 × 10â»4 to 3.96 × 10â»7). We validated the association by genotyping 5 SNPs from the DPA1/DPB1 region in an additional cohort and obtained P values from 6.42 × 10â»5 to 0.01 in the analysis of the combined cohorts. Subtyping analysis of HLA-DPA1 and HLA-DPB1 showed that HLA-DPA1*0103, A1*0201, and B1*1301 were the subtypes most susceptible to AS.CONCLUSION:
HLA markers and linkage disequilibrium blocks near HLA-DPA1 and HLA-DPB1 are statistically associated with AS. We identified a region located around the HLA-DPA1 and HLA-DPB1 loci associated with AS, another region within the MHC that is different from HLA-B27.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espondilite Anquilosante
/
Cadeias alfa de HLA-DP
/
Cadeias beta de HLA-DP
/
Complexo Principal de Histocompatibilidade
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article