Genetic and genomic studies of PADI4 in rheumatoid arthritis

Harney, S. M. J., Meisel, C., Sims, A. M., Woon, P. Y., Wordsworth, B. P., & Brown, M. A. (2005) Genetic and genomic studies of PADI4 in rheumatoid arthritis. Rheumatology, 44(7), pp. 869-872.

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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_04) 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.

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44 citations in Web of Science®
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ID Code: 89483
Item Type: Journal Article
Refereed: Yes
Keywords: Anti-CCP antibodies, Genetic polymorphism, Real-time PCR, nucleotide, protein arginine deiminase, RNA, autoantibody, biological marker, cyclic citrullinated peptide, cyclopeptide, hydrolase, peptidylarginine deiminase type IV, article, case control study, Caucasian, controlled study, correlation function, data analysis, gene overexpression, genetic association, genetic transcription, genetic variability, genomics, genotype, haplotype, human, human cell, major clinical study, microsatellite marker, peripheral blood mononuclear cell, polymerase chain reaction, priority journal, protein blood level, protein expression, quantitative analysis, real time polymerase chain reaction, restriction fragment length polymorphism, rheumatoid arthritis, risk factor, RNA extraction, single nucleotide polymorphism, statistical significance, United Kingdom, blood, enzymology, genetics, immunology, Arthritis, Rheumatoid, Autoantibodies, Biological Markers, Case-Control Studies, Humans, Hydrolases, Peptides, Cyclic, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide
DOI: 10.1093/rheumatology/keh614
ISSN: 1462-0324
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2008 The Authors
Deposited On: 25 Oct 2015 23:29
Last Modified: 26 Oct 2015 00:42

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