TY - JOUR
T1 - Association of rheumatoid arthritis risk alleles with response to anti-TNF biologics
T2 - Results from the CORRONA registry and meta-analysis
AU - Pappas, Dimitrios A.
AU - Oh, Cheongeun
AU - Plenge, Robert M.
AU - Kremer, Joel M.
AU - Greenberg, Jeffrey D.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/4
Y1 - 2013/4
N2 - In this study, we investigated whether genetic variants known to be related with susceptibility to rheumatoid arthritis (RA) are also associated with response to therapy with anti-tumor necrosis factor (anti-TNF) biologics; 233 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry were studied. Findings were combined with results from an international collaborative study (N = 1,283) in a meta-analysis (N = 1,516). Multivariate models investigating the association between single nucleotide polymorphisms (SNPs) and change in RA disease activity were adjusted for age, gender, concomitant methotrexate, and baseline disease activity. In the CORRONA cohort, nominal associations with disease activity improvement were observed for the rs1980422 SNP of the CD28 gene in multivariate models (coefficient -0.377, p = 0.005) but were not significant after adjustment for multiple comparisons (q = 0.10). In the meta-analysis, the only SNP with nominal associations with change in DAS28 was the rs2812378 SNP of the CCL21 gene (coefficient 1.9195, p = 0.0068). This association was not significant after adjustment for multiple comparisons (q = 0.143). We conclude that the established RA risk alleles studied were not significantly associated with response to anti-TNF biologics in the CORRONA cohort or the meta-analysis.
AB - In this study, we investigated whether genetic variants known to be related with susceptibility to rheumatoid arthritis (RA) are also associated with response to therapy with anti-tumor necrosis factor (anti-TNF) biologics; 233 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry were studied. Findings were combined with results from an international collaborative study (N = 1,283) in a meta-analysis (N = 1,516). Multivariate models investigating the association between single nucleotide polymorphisms (SNPs) and change in RA disease activity were adjusted for age, gender, concomitant methotrexate, and baseline disease activity. In the CORRONA cohort, nominal associations with disease activity improvement were observed for the rs1980422 SNP of the CD28 gene in multivariate models (coefficient -0.377, p = 0.005) but were not significant after adjustment for multiple comparisons (q = 0.10). In the meta-analysis, the only SNP with nominal associations with change in DAS28 was the rs2812378 SNP of the CCL21 gene (coefficient 1.9195, p = 0.0068). This association was not significant after adjustment for multiple comparisons (q = 0.143). We conclude that the established RA risk alleles studied were not significantly associated with response to anti-TNF biologics in the CORRONA cohort or the meta-analysis.
KW - TNF-alpha inhibitors
KW - pharmacogenetics
KW - rheumatoid arthritis
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U2 - 10.1007/s10753-012-9544-4
DO - 10.1007/s10753-012-9544-4
M3 - Article
C2 - 23007924
AN - SCOPUS:84879502298
SN - 0360-3997
VL - 36
SP - 279
EP - 284
JO - Inflammation
JF - Inflammation
IS - 2
ER -