Journal
PHARMACOGENETICS AND GENOMICS
Volume 19, Issue 4, Pages 319-323Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0b013e328328d51f
Keywords
anti-tumour necrosis factor; association; candidate; gene; pathway; response; rheumatoid arthritis
Funding
- Arthritis Research Campaign [17552]
- Medical Research Council [G9818340B] Funding Source: researchfish
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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.
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