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Rheumatology Advance Access published online on April 6, 2005
Rheumatology, doi:10.1093/rheumatology/keh614
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received October 28, 2004
Accepted February 22, 2005

Concise Report

Genetic and genomic studies of PADI4 in rheumatoid arthritis

S. M. J. Harney 1, C. Meisel 1, A.-M. Sims 1, P. Y. Woon 2, B. P. Wordsworth 1, and M. A. Brown 1*

1 Institute of Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Oxford, UK
2 Wellcome Trust Centre for Human Genetics, Oxford, UK

* To whom correspondence should be addressed.
M. A. Brown, E-mail: mbrown{at}well.ox.ac.uk


  Abstract

Objectives. Strong genetic association of rheumatoid arthritis (RA) with PADI4 (peptidyl arginine deiminase) has previously been described in Japanese, although this was not confirmed in a subsequent study in the UK. We therefore undertook a further study of genetic association between PADI4 and RA in UK Caucasians and also studied expression of PADI4 in the peripheral blood of patients with RA.

Methods. Seven single-nucleotide polymorphisms (SNP) were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism in 111 RA cases and controls. A marker significantly associated with RA (PADI4_100, rs#2240339) in this first data set (P = 0.03) was then tested for association in a larger group of 439 RA patients and 428 controls. PADI4 transcription was also assessed by real-time quantitative PCR using RNA extracted from peripheral blood mononuclear cells from 13 RA patients and 11 healthy controls.

Results. A single SNP was weakly associated with RA (P = 0.03) in the initial case-control study, a single SNP (PADI4_100) and a two marker haplotype of that SNP and the neighbouring SNP (PADI4_104) were significantly associated with RA (P = 0.02 and P = 0.03 respectively). PADI4_100 was not associated with RA in a second sample set. PADI4 expression was four times greater in cases than controls (P = 0.004), but expression levels did not correlate with the levels of markers of inflammation.

Conclusion. PADI4 is significantly overexpressed in the blood of RA patients but genetic variation within PADI4 is not a major risk factor for RA in Caucasians.

Keywords: Real-time PCR; Anti-CCP antibodies; Genetic polymorphism.
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T. Iwamoto, K. Ikari, T. Nakamura, M. Kuwahara, Y. Toyama, T. Tomatsu, S. Momohara, and N. Kamatani
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Rheumatology, July 1, 2006; 45(7): 804 - 807.
[Abstract] [Full Text] [PDF]


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