Interleukin-6-receptor polymorphisms rs12083537, rs2228145, and rs4329505 as predictors of response to tocilizumab in rheumatoid arthritis.
Pharmacogenet Genomics
; 24(8): 401-5, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24978393
ABSTRACT
Tocilizumab (TCZ), a monoclonal antibody targeting the human interleukin-6-receptor (IL-6R), is indicated for the treatment of rheumatoid arthritis (RA). We examined whether three IL6R single-nucleotide polymorphisms rs12083537, rs2228145 (formerly rs8192284), and rs4329505 with previously reported functional effects were associated with clinical response to TCZ in a retrospective study cohort consisting of 79 RA patients. Three months after initiation of TCZ therapy, changes in swollen joint count (SJC) and, subordinately, tender joint count (TJC), serum-CRP, DAS28-CRP, and EULAR-response were tested for association with the IL6R-haplotype or genotype. The major allele (A) of rs12083537 and the minor allele (C) of rs4329505 were associated with a poor SJC response (P=0.02 and 0.02, respectively). Moreover, the AAC-haplotype (for rs12083537, rs2228145, and rs4329505, respectively) was associated with a poor SJC response (P=0.00004) and, with borderline significance, EULAR-response (P=0.05). These data suggest that genetic variation in IL6R may aid in predicting TCZ therapy outcome in RA patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
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Receptores de Interleucina-6
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Polimorfismo de Nucleotídeo Único
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Anticorpos Monoclonais Humanizados
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article