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.
Crisp AJ, Gaston JS, Hall FC, Hazleman BL, Jenner JR, Ostor A, Silverman B, Speed C, Armstrong D, Chuck AJ, Hailwood S, Badcock LJ, Deighton CM, O'Reilly SC, Regan MR, Snaith, Summers GD, Williams RA, Lambert JR, Stevens R, Wilkinson C, Hamilton J, Heycock CR, Kelly CA, Saravanan V, Rees DH, Williams RB, Chalam SV, Mulherin D, Price T, Sheeran T, Bukhari M, Dodds WN, Halsey JP, Gaffney K, Macgregor AJ, Marshall T, Merry P, Scott DG, Harrison B, Pattrick M, Snowden HN, Sheehan NJ, Williams NE, Hull RG, Ledingham JM, McCrae F, Shaban MR, Thomas AL, Buckley CD, Carruthers DC, Elamanchi R, Gordon PC, Grindulis KA, Khattak F, Raza K, Situnayake D, Akil M, Amos R, Bax DE, Till S, Wilson G, Winfield J, Clarke F, Fordham JN, Plant MJ, Tuck, Abernethy VE, Dawson JK, Lynch M, Bingham S, Emery P, Morgan A, Birrell F, Crook P, Foster HE, Griffiths B, Griffiths ID, Grove ML, Isaacs JD, Kay L, Myers A, Platt PN, Walker DJ, Bowman, Jobanputra P, Jubb RW, Rankin EC, Carpenter EH, Dawes PT, Hassell A, Hay EM, Kamath S, Packham J, Shadforth MF, Donnelly SP, Doyle D, Hakim A, Lanham JG.
Source
Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK. j.bowes@manchester.ac.uk
Abstract
The introduction of anti-tumour necrosis factor (TNF) agents has greatly improved the treatment of rheumatoid arthritis; however, a significant proportion of patients fail to respond to therapy. We hypothesized that genes within the TNF receptor superfamily member 1B 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 not 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.
- PMID:
- 19262425
- [PubMed - indexed for MEDLINE]
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