Document Detail


CD6 and syntaxin binding protein 6 variants and response to tumor necrosis factor alpha inhibitors in Danish patients with rheumatoid arthritis.
MedLine Citation:
PMID:  22685579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: TNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFα inhibitors in patients with rheumatoid arthritis (RA).
METHODOLOGY AND PRINCIPAL FINDINGS: In the DANBIO Registry we identified 237 TNFα inhibitor naïve patients with RA (81% women; median age 56 years; disease duration 6 years) who initiated treatment with infliximab (n=160), adalimumab (n=56) or etanercept (n=21) between 1999 and 2008 according to national treatment guidelines. Clinical response was assessed at week 26 using EULAR response criteria. Based on literature, we selected 213 INDELS potentially related to RA and treatment response using the GeneVa® (Compugen) in silico database of 350,000 genetic variations in the human genome. Genomic segments were amplified by polymerase chain reaction (PCR), and genotyped by Sanger sequencing or fragment analysis. We tested the association between genotypes and EULAR good response versus no response, and EULAR good response versus moderate/no response using Fisher's exact test. At baseline the median DAS28 was 5.1. At week 26, 68 (29%) patients were EULAR good responders, while 81 (34%) and 88 (37%) patients were moderate and non-responders, respectively. A 19 base pair insertion within the CD6 gene was associated with EULAR good response vs. no response (OR=4.43, 95% CI: 1.99-10.09, p=7.211×10(-5)) and with EULAR good response vs. moderate/no response (OR=4.54, 95% CI: 2.29-8.99, p=3.336×10(-6)). A microsatellite within the syntaxin binding protein 6 (STXBP6) was associated with EULAR good response vs. no response (OR=4.01, 95% CI: 1.92-8.49, p=5.067×10(-5)).
CONCLUSION: Genetic variations within CD6 and STXBP6 may influence response to TNFα inhibitors in patients with RA.
Authors:
Sophine B Krintel; Laurent Essioux; Assaf Wool; Julia S Johansen; Ehud Schreiber; Tomer Zekharya; Pinchas Akiva; Mikkel Ostergaard; Merete L Hetland
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-07
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-11     Completed Date:  2012-12-07     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e38539     Citation Subset:  IM    
Affiliation:
DANBIO Registry and Department of Rheumatology, Copenhagen University Hospital at Glostrup, Copenhagen, Denmark. krintel@sophine.dk
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized / therapeutic use
Antigens, CD / genetics*
Antigens, Differentiation, T-Lymphocyte / genetics*
Antirheumatic Agents / therapeutic use*
Arthritis, Rheumatoid / drug therapy*,  genetics*
Carrier Proteins / genetics*
Cohort Studies
DNA Mutational Analysis
Denmark
Female
Genotype
Humans
INDEL Mutation*
Immunoglobulin G / therapeutic use
Male
Middle Aged
Polymerase Chain Reaction
Receptors, Tumor Necrosis Factor / therapeutic use
Treatment Outcome
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Young Adult
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antigens, CD; 0/Antigens, Differentiation, T-Lymphocyte; 0/Antirheumatic Agents; 0/CD6 antigen; 0/Carrier Proteins; 0/Immunoglobulin G; 0/Receptors, Tumor Necrosis Factor; 0/STXBP6 protein, human; 0/Tumor Necrosis Factor-alpha; 0/infliximab; 185243-69-0/TNFR-Fc fusion protein; FYS6T7F842/adalimumab
Comments/Corrections

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