A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis

被引：27

作者：

Julia, A. ^{[1
]}

Fernandez-Nebro, A. ^{[2
]}

Blanco, F. ^{[3
]}

Ortiz, A. ^{[4
]}

Canete, J. D. ^{[5
]}

Maymo, J. ^{[6
]}

Alperi-Lopez, M. ^{[7
]}

Fernandez-Gutierrez, B. ^{[8
]}

Olive, A. ^{[9
]}

Corominas, H. ^{[10
]}

Erra, A. ^{[11
]}

Acosta-Colman, I. ^{[1
]}

Alonso, A. ^{[1
]}

Lopez-Lasanta, M. ^{[1
]}

Tortosa, R. ^{[1
]}

Tornero, J. ^{[12
]}

Marsal, S. ^{[1
]}

机构：

[1] Vall dHebron Hosp Res Inst, Rheumatol Res Grp, Pg Vall Hebron 119-129, Barcelona 08035, Spain

[2] Univ Malaga, Hosp Reg Univ Malaga, Inst Invest Biomed Malaga IBIMA, UGC Reumatol, E-29071 Malaga, Spain

[3] INIBIC Hosp Univ A Coruna, Rheumatol Serv, La Coruna, Spain

[4] IIS La Princesa, IIS Princesa, Hosp Univ La Princesa, Rheumatol Serv, Madrid, Spain

[5] Hosp Clin Barcelona, Rheumatol Serv, Barcelona, Spain

[6] Hosp del Mar, Rheumatol Serv, Barcelona, Spain

[7] Hosp Univ Cent Asturias, Rheumatol Serv, Oviedo, Spain

[8] Hosp Clin San Carlos, Rheumatol Serv, Madrid, Spain

[9] Hosp Badalona Germans Trias & Pujol, Rheumatol Serv, Barcelona, Spain

[10] Hosp Moises Broggi, Rheumatol Serv, Barcelona, Spain

[11] Hosp St Rafael, Rheumatol Serv, Barcelona, Spain

[12] Hosp Univ Guadalajara, Rheumatol Serv, Guadalajara, Spain

来源：

PHARMACOGENOMICS JOURNAL | 2016年 / 16卷 / 02期

关键词：

EXPRESSION; POLYMORPHISMS; REPLICATION; INFLIXIMAB; PREDICTS; CELLS;

D O I：

10.1038/tpj.2015.31

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Anti-Tumor Necrosis Factor (anti-TNF) drugs are biologic agents commonly used to treat rheumatoid arthritis (RA). However, anti-TNFs are not effective in approximately one out of four treated patients. We conducted a Genome-Wide Association Study (GWAS) to identify the genetic variation associated with the response to anti-TNF therapy in RA. In the discovery stage, 372 RA patients treated with an anti-TNF agent (infliximab, adalimumab or etanercept) were analyzed and treatment response was defined at 12 weeks of therapy. We found a genome-wide significant association in the MED15 gene with the response to etanercept (P<1.5e-8). Using an independent cohort of 245 RA patients, we performed a replication study of the most significant GWAS associations. We replicated the association at the MED15 locus and found suggestive evidence of association in the previously associated MAFB locus. The results of this study suggest novel mechanisms associated with the response to anti-TNF therapies.

引用

页码：147 / 150

页数：4

共 37 条

[1]

Acosta-Colman I, 2013, PHARMACOGENOMICS, V14, P727, DOI [10.2217/PGS.13.60, 10.2217/pgs.13.60]

[2]

GStream: Improving SNP and CNV Coverage on Genome-Wide Association Studies [J].

Alonso, Arnald ;

Marsal, Sara ;

Tortosa, Rauel ;

Canela-Xandri, Oriol ;

Julia, Antonio .

PLOS ONE, 2013, 8 (07)

[3]

An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[4]

THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].

ARNETT, FC ;

EDWORTHY, SM ;

BLOCH, DA ;

MCSHANE, DJ ;

FRIES, JF ;

COOPER, NS ;

HEALEY, LA ;

KAPLAN, SR ;

LIANG, MH ;

LUTHRA, HS ;

MEDSGER, TA ;

MITCHELL, DM ;

NEUSTADT, DH ;

PINALS, RS ;

SCHALLER, JG ;

SHARP, JT ;

WILDER, RL ;

HUNDER, GG .

ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324

[5]

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis [J].

Cui, Jing ;

Stahl, Eli A. ;

Saevarsdottir, Saedis ;

Miceli, Corinne ;

Diogo, Dorothee ;

Trynka, Gosia ;

Raj, Towfique ;

Mirkov, Masa Umicevic ;

Canhao, Helena ;

Ikari, Katsunori ;

Terao, Chikashi ;

Okada, Yukinori ;

Wedren, Sara ;

Askling, Johan ;

Yamanaka, Hisashi ;

Momohara, Shigeki ;

Taniguchi, Atsuo ;

Ohmura, Koichiro ;

Matsuda, Fumihiko ;

Mimori, Tsuneyo ;

Gupta, Namrata ;

Kuchroo, Manik ;

Morgan, Ann W. ;

Isaacs, John D. ;

Wilson, Anthony G. ;

Hyrich, Kimme L. ;

Herenius, Marieke ;

Doorenspleet, Marieke E. ;

Tak, Paul-Peter ;

Crusius, J. Bart A. ;

van der Horst-Bruinsma, Irene E. ;

Wolbink, Gert Jan ;

van Riel, Piet L. C. M. ;

van de Laar, Mart ;

Guchelaar, Henk-Jan ;

Shadick, Nancy A. ;

Allaart, Cornelia F. ;

Huizinga, Tom W. J. ;

Toes, Rene E. M. ;

Kimberly, Robert P. ;

Bridges, S. Louis, Jr. ;

Criswell, Lindsey A. ;

Moreland, Larry W. ;

Fonseca, Joao Eurico ;

de Vries, Niek ;

Stranger, Barbara E. ;

De Jager, Philip L. ;

Raychaudhuri, Soumya ;

Weinblatt, Michael E. ;

Gregersen, Peter K. .

PLOS GENETICS, 2013, 9 (03)

[6]

Delaneau O, 2012, NAT METHODS, V9, P179, DOI [10.1038/NMETH.1785, 10.1038/nmeth.1785]

[7]

IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial [J].

Emery, P. ;

Keystone, E. ;

Tony, H. P. ;

Cantagrel, A. ;

van Vollenhoven, R. ;

Sanchez, A. ;

Alecock, E. ;

Lee, J. ;

Kremer, J. .

ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (11) :1516-1523

[8]

Evolving concepts of rheumatoid arthritis [J].

Firestein, GS .

NATURE, 2003, 423 (6937) :356-361

[9]

Fransen J, 2005, CLIN EXP RHEUMATOL, V23, pS93

[10]

Virally mediated MafB transduction induces the monocyte commitment of human CD34+hematopoietic stem/progenitor cells [J].

Gemelli, C. ;

Montanari, M. ;

Tenedini, E. ;

Marani, T. Zanocco ;

Vignudelli, T. ;

Siena, M. ;

Zini, R. ;

Salati, S. ;

Tagliafico, E. ;

Manfredini, R. ;

Grande, A. ;

Ferrari, S. .

CELL DEATH AND DIFFERENTIATION, 2006, 13 (10) :1686-1696

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