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.
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.
Bowes
John D
JD
Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK. j.bowes@manchester.ac.uk
Potter
Catherine
C
Gibbons
Laura J
LJ
Hyrich
Kimme
K
Plant
Darren
D
Morgan
Ann W
AW
Wilson
Anthony G
AG
Isaacs
John D
JD
Worthington
Jane
J
Barton
Anne
A
D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D015398:Signal Transduction; D006113:United Kingdom
D018501:Antirheumatic Agents; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human