Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis.
Arthritis Rheum
; 60(8): 2242-7, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19644859
ABSTRACT
OBJECTIVE:
The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. The purpose of this study was to investigate whether these newly described genetic regions are associated with the rate of joint destruction.METHODS:
RA patients enrolled in the Leiden Early Arthritis Clinic were studied (n=563). Yearly radiographs were scored using the Sharp/van der Heijde method (median followup 5 years; maximum followup 9 years). The rate of joint destruction between genotype groups was compared using a linear mixed model, correcting for age, sex, and treatment strategies. A total of 393 anti-citrullinated protein antibody (ACPA)-positive RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) who had radiographic data available were used for the replication study.RESULTS:
The TT and CC/CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 (CD40) and rs42041 (CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P=0.003 and P=0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. The association of the CD40 minor allele with the rate of radiographic progression was replicated in the NARAC cohort (P=0.021).CONCLUSION:
A polymorphism in the CD40 locus is associated with the rate of joint destruction in patients with ACPA-positive RA. Our findings provide one of the first non-HLA-related genetic severity factors that has been replicated.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
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Antígenos CD40
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Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
/
Systematic_reviews
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article