CD6 and Syntaxin Binding Protein 6 Variants and Response to Tumor Necrosis Factor Alpha Inhibitors in Danish Patients with Rheumatoid Arthritis

被引：19

作者：

Krintel, Sophine B. ^{[1
,2
]}

Essioux, Laurent ^{[3
]}

Wool, Assaf ^{[4
]}

Johansen, Julia S. ^{[5
,6
,7
]}

Schreiber, Ehud ^{[4
]}

Zekharya, Tomer ^{[4
]}

Akiva, Pinchas ^{[4
]}

Ostergaard, Mikkel ^{[1
,2
,7
]}

Hetland, Merete L. ^{[1
,2
,7
]}

机构：

[1] Copenhagen Univ Hosp Glostrup, DANBIO Registry, Copenhagen, Denmark

[2] Copenhagen Univ Hosp Glostrup, Dept Rheumatol, Copenhagen, Denmark

[3] Hoffmann La Roche Ag, CH-4002 Basel, Switzerland

[4] Compugen Ltd, Tel Aviv, Israel

[5] Univ Copenhagen, Copenhagen Univ Hosp Herlev, Dept Med, Copenhagen, Denmark

[6] Univ Copenhagen, Copenhagen Univ Hosp Herlev, Dept Oncol, Copenhagen, Denmark

[7] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark

来源：

PLOS ONE | 2012年 / 7卷 / 06期

关键词：

ANTI-TNF TREATMENT; GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; DIFFERENTIAL RESPONSE; CANDIDATE GENES; THERAPY; METHOTREXATE; ADALIMUMAB; INFLIXIMAB; RECEPTOR;

D O I：

10.1371/journal.pone.0038539

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: TNF alpha 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 TNF alpha inhibitors in patients with rheumatoid arthritis (RA). Methodology and Principal Findings: In the DANBIO Registry we identified 237 TNF alpha inhibitor naive 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 (R) (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 x 10(-5)) and with EULAR good response vs. moderate/no response (OR = 4.54, 95% CI: 2.29-8.99, p = 3.336 x 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 x 10(-5)). Conclusion: Genetic variations within CD6 and STXBP6 may influence response to TNF alpha inhibitors in patients with RA.

引用

页数：8

共 46 条

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