The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosive disease in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register.
OBJECTIVE
Recent whole-genome and candidate gene association studies in RA have identified a number of single nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. It remains poorly understood how recently identified genetic factors may contribute to RA severity. We therefore sought to investigate the role of recently identified RA susceptibility SNP markers in predicting erosive outcome in patients with recent-onset inflammatory polyarthritis (IP).


METHODS
DNA and X-ray data were available for 1049 patients who were registered between 1990 and 2003 with the Norfolk Arthritis Register (NOAR); a primary care-based inception cohort of patients with recent-onset IP. Demographic and clinical data were recorded at inclusion, and at yearly assessments thereafter. Patients were genotyped for 18 SNP markers. The presence of serum anti citrullinated peptide antibodies (ACPAs) was assessed in samples collected at inclusion to the NOAR. The association of serological and genetic markers with poor radiological (Larsen) score at Years 1 and 5, and erosions at Years 1 and 5 was investigated.


RESULTS
Baseline ACPA positivity was associated with erosive disease and higher radiological damage. SNP markers within the TRAF1/C5 locus were associated with erosive disease at Year 1 [rs2900180: odds ratio (OR) 1.53 (95% CI 1.14, 2.05)] and Year 5 [rs2900180: OR 1.47 (95% CI 1.07, 2.02)]. None of the SNP markers tested was associated with Larsen score.


CONCLUSIONS
Our results are in keeping with a previous report and suggest that the TRAF1/C5 region is associated with risk of development of radiological erosions in IP/RA patients. The finding requires replication in other large data sets.
Plant
Darren
D
ARC Epidemiology Unit, Manchester Academic Health Sciences Centre, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Thomson
Wendy
W
Lunt
Mark
M
Flynn
Edward
E
Martin
Paul
P
Eyre
Steven
S
Farragher
Tracey
T
Bunn
Diane
D
Worthington
Jane
J
Symmons
Deborah
D
Barton
Anne
A
D000328:Adult; D017668:Age of Onset; D001168:Arthritis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index
D005819:Genetic Markers