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Association of the tumour necosis factor -308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis

Lookup NU author(s): Dr Kate Potter, Professor John Isaacs

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Abstract

Anti-tumour necrosis factor (TNF) agents have revolutionised the treatment of patients with Rheumatoid Arthritis (RA). These therapies are however expensive and 30% of patients fail to respond. In a large cohort of Caucasian RA patients treated with anti-TNF medications (total n=1050, etanercept n=455, infliximab n=450) we investigated whether genotypes of eight single nucleotide polymorphisms (SNPs) in the region containing the TNF gene were associated with response to anti-TNF therapy. Linear regression analyses adjusted for baseline 28 joint disease activity score (DAS28), baseline health assessment questionnaire (HAQ) score, gender and concurrent disease modifying anti-rheumatic drug (DMARD) treatment, were used to assess association of these polymorphisms with treatment response, defined by change in DAS28 after 6 months. Analyses were performed in the entire cohort, and also stratified by anti-TNF agent. Association between DAS28 response and TNF-308 (rs1800629) genotype (p=0.001) was detected across the whole cohort. After stratification by anti-TNF agent, the rare TNF-308AA genotype was associated with a significantly poorer response compared with TNF-308GG in etanercept (p=0.001, n=7) but not infliximab (p=0.8, n=17) treated patients. Conversely, the GA genotype at TNF-238 (rs361525) was associated with a poorer response to infliximab (p=0.028 n=40), but not etanercept (p=0.6 n=33). Due to the small numbers of patients in some of the genotype groups examined, our data must be regarded as preliminary and will require replication in further large cohorts of anti-TNF treated patients. If confirmed our findings suggest the potential for genotype at these markers to aid selection of anti-TNF agent in patients with RA.


Publication metadata

Author(s): Maxwell JR, Potter C, Hyrich KL, Barton A, Worthington J, Isaacs JD, Morgan AW, Wilson AG

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2008

Volume: 17

Issue: 22

Pages: 3532-3538

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/hmg/ddn245

DOI: 10.1093/hmg/ddn245

Notes: Braggss Journal article


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