Genetic Variants in Toll-Like Receptors Are Not Associated with Rheumatoid Arthritis Susceptibility or Anti-Tumour Necrosis Factor Treatment Outcome

被引：25

作者：

Coenen, Marieke J. H. ^{[1
]}

Enevold, Christian ^{[2
]}

Barrera, Pilar ^{[3
]}

Schijvenaars, Mascha M. V. A. P. ^{[1
]}

Toonen, Erik J. M. ^{[1
]}

Scheffer, Hans ^{[1
]}

Padyukov, Leonid ^{[4
]}

Kastbom, Alf ^{[5
]}

Klareskog, Lars ^{[4
]}

Barton, Anne ^{[6
]}

Kievit, Wietske

Rood, Maarten J. ^{[7
]}

Jansen, Tim L. ^{[8
]}

Swinkels, Dorine ^{[9
]}

van Riel, Piet L. C. M. ^{[3
]}

Franke, Barbara ^{[1
]}

Bendtzen, Klaus ^{[2
]}

Radstake, Timothy R. D. J. ^{[3
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, IGMD, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[2] Univ Copenhagen Hosp, Rigshosp, Inst Inflammat Res, Dept Rheumatol, DK-2100 Copenhagen, Denmark

[3] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands

[4] Karolinska Inst, Karolinska Univ Hosp Solna, Dept Med, Rheumatol Unit, Stockholm, Sweden

[5] Linkoping Univ, Dept Clin & Expt Med, Div Rheumatol, Linkoping, Sweden

[6] Univ Manchester, Arthrit Res Campaign Epidemiol Unit, Manchester, Lancs, England

[7] Ziekenhuis Gelderse Vallei, Dept Rheumatol, Ede, Netherlands

[8] Med Ctr Leeuwarden, Dept Rheumatol, Leeuwarden, Netherlands

[9] Radboud Univ Nijmegen, Clin Chem Lab, Med Ctr, NL-6525 ED Nijmegen, Netherlands

来源：

PLOS ONE | 2010年 / 5卷 / 12期

关键词：

SINGLE NUCLEOTIDE POLYMORPHISM; GENOME-WIDE ASSOCIATION; DISEASE SEVERITY; TOLL-LIKE-RECEPTOR-4; POPULATION; EXPRESSION; RISK;

D O I：

10.1371/journal.pone.0014326

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background: Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication. Methodology and Principal Findings: 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population. Conclusion: We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population.

引用

页数：6

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