Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis.
BACKGROUND
A functional haplotype of the peptidylarginine deiminase 4 (PADI4) gene has recently been identified as a rheumatoid arthritis susceptibility gene in a Japanese but not in a UK population. One possible explanation for this disparity is that the gene determines severity of rather than susceptibility to inflammatory polyarthritis (IP) and that the UK and Japanese cohorts differed in terms of outcome.


OBJECTIVE
To examine the association between individual PADI4 single nucleotide polymorphisms (SNPs) and haplotypes, with the development and severity of erosions by five years in patients with IP.


METHODS
438 patients from the NOAR inception cohort of patients with IP were x rayed five years after presentation with early IP. Association with four exonic SNPs (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and defining a haplotype previously reported to be associated with rheumatoid arthritis, was investigated. Patients were compared for the presence, extent, and progression of erosions by five years and the presence of antibodies to citrullinated peptide (anti-CCP antibodies).


RESULTS
There was no association between individual PADI4 SNPs or haplotypes and the development or extent of erosions by five years. Restricting analysis to patients who satisfied ACR criteria for rheumatoid arthritis by five years did not alter the conclusions. No association with presence of anti-CCP antibodies was detected.


CONCLUSIONS
No evidence was found for association of the PADI4 gene with severity as assessed by erosive outcome at five years or with presence of anti-CCP antibodies in patients with IP.
Barton
A
A
ARC-EU, Stopford Building, University of Manchester, Manchester M13 9PT, UK. anne.barton@manchester.ac.uk
Bowes
J
J
Eyre
S
S
Symmons
D
D
Worthington
J
J
Silman
A
A
D000328:Adult; D000368:Aged; D001168:Arthritis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D011859:Radiography; D012720:Severity of Illness Index
D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
Rheumatology (Oxford). 2000 Jun;39 Suppl 1:9-16
11001374
Ann Rheum Dis. 2005 Apr;64(4):587-93
15485997
Arthritis Rheum. 2002 Apr;46(4):906-12
11953966
Curr Opin Rheumatol. 2002 May;14(3):250-3
11981322
Ann Rheum Dis. 2003 Feb;62(2):120-6
12525380
Rheumatology (Oxford). 2003 May;42(5):677-80
12709545
J Rheumatol. 2003 May;30(5):902-4
12734878
Nat Genet. 2003 Aug;34(4):395-402
12833157
Arthritis Rheum. 2004 Mar;50(3):709-15
15022309
Arthritis Rheum. 2004 Apr;50(4):1117-21
15077293
Arthritis Rheum. 1989 Feb;32(2):221-9
2645876
Arthritis Rheum. 1990 Jul;33(7):1042-6
2369420
Br J Rheumatol. 1994 Aug;33(8):735-9
8055200
J Rheumatol. 1994 Aug;21(8):1420-6
7983640
Arthritis Rheum. 1999 Oct;42(10):2174-83
10524690
J Mol Med (Berl). 2004 Nov;82(11):762-7
15338034
Arthritis Rheum. 2002 Feb;46(2):357-65
11840437