Investigation of genetic variants within candidate genes of the TNFRSF1B signalling pathway on the response to anti-TNF agents in a UK cohort of rheumatoid arthritis patients

被引：30

作者：

Bowes, John D. ^{[1
]}

Potter, Catherine ^{[5
]}

Gibbons, Laura J. ^{[1
]}

Hyrich, Kimme ^{[1
]}

Plant, Darren ^{[1
]}

Morgan, Ann W. ^{[3
]}

Wilson, Anthony G. ^{[4
]}

Isaacs, John D. ^{[5
]}

Worthington, Jane ^{[1
]}

Barton, Anne ^{[1
]}

机构：

[1] Univ Manchester, Arthrit Res Campaign Epidemiol Unit, Manchester M13 9PT, Lancs, England

[2] Univ Leeds, Biol Rheumatoid Arthrit Genet & Genom Study Syndi, Leeds, W Yorkshire, England

[3] Univ Leeds, Leeds Inst Mol Med, Leeds, W Yorkshire, England

[4] Univ Sheffield, Sect Musculoskeletal Sci, Sheffield, S Yorkshire, England

[5] Univ Newcastle, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England

来源：

PHARMACOGENETICS AND GENOMICS | 2009年 / 19卷 / 04期

关键词：

anti-tumour necrosis factor; association; candidate; gene; pathway; response; rheumatoid arthritis; ANTITUMOR NECROSIS FACTOR; BIOLOGICS-REGISTER; BRITISH-SOCIETY; CONCOMITANT METHOTREXATE; MONOCLONAL-ANTIBODY; FACTOR THERAPY; TRIAL; INFLIXIMAB;

D O I：

10.1097/FPC.0b013e328328d51f

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The introduction of anti-tumour necrosis factor (TNF) agents has greatly improved the treatment of rheumatoid arthritis; however, a significant proportion of patients fall to respond to therapy. We hypothesized that genes within the TNF receptor superfamily member 1 B signalling pathway contribute towards the observed variation in patient response. This was tested by genotyping 73 single-nucleotide polymorphisms (SNPs) from six candidate genes (DUSP1, HRB, IKBKAP, MAP3K1, MAP3K14 and TANK) in a large UK cohort of rheumatoid arthritis patients (n=642). Two SNPs [rs96844(MAP3K1) and rs4792847 (MAP3K14)] showed evidence of association (P<0.05) to treatment response and were subsequently examined in an independent cohort of patients (n=428). Replication of association to either SNP was hot achieved, but combined analysis of the complete cohort (n=1070) provided nominal evidence of association to both SNPs. We conclude that analysis of the common variation in the selected candidate genes did not provide strong evidence to implicate their involvement in varying patient response to anti-TNF treatment. Pharmacogenetics and Genomics 19:319-323 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

引用

页码：319 / 323

页数：5

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