Rheumatology Advance Access originally published online on April 6, 2005
Rheumatology 2005 44(7):869-872; doi:10.1093/rheumatology/keh614
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Genetic and genomic studies of PADI4 in rheumatoid arthritis
Institute of Musculoskeletal Sciences, University of Oxford, Botnar Research Centre and 1 Wellcome Trust Centre for Human Genetics, Oxford, UK.
Correspondence to: M. A. Brown, University of Oxford, Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD, UK. E-mail: mbrown{at}well.ox.ac.uk
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Abstract |
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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.
KEY WORDS: Real-time PCR, Anti-CCP antibodies, Genetic polymorphism
Submitted 28 October 2004;
revised version accepted 22 February 2005.
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