A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis.
Ann Rheum Dis
; 71(5): 714-7, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22294640
ABSTRACT
OBJECTIVE:
To identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations.METHODS:
High-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive.RESULTS:
Two markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10(-3)) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19 59347459-59356564, p=2.43 × 10(-4) to 6.54 × 10(-4)). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73 × 10(-6)). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS.CONCLUSION:
A novel significant association was detected between SNP rs1055234 and AS susceptibility.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espondilite Anquilosante
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Fatores de Transcrição
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Cromossomos Humanos Par 19
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Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article