Genetic and genomic studies of PADI4 in rheumatoid arthritis.
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...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2005
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| _version_ | 1826271390375870464 |
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| author | Harney, S Meisel, C Sims, A Woon, P Wordsworth, B Brown, M |
| author_facet | Harney, S Meisel, C Sims, A Woon, P Wordsworth, B Brown, M |
| author_sort | Harney, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:55:55Z |
| format | Journal article |
| id | oxford-uuid:4ceef9a8-ba70-42e7-9846-0bbe726ca89a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:55:55Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:4ceef9a8-ba70-42e7-9846-0bbe726ca89a2022-03-26T15:52:23ZGenetic and genomic studies of PADI4 in rheumatoid arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4ceef9a8-ba70-42e7-9846-0bbe726ca89aEnglishSymplectic Elements at Oxford2005Harney, SMeisel, CSims, AWoon, PWordsworth, BBrown, MOBJECTIVES: 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. |
| spellingShingle | Harney, S Meisel, C Sims, A Woon, P Wordsworth, B Brown, M Genetic and genomic studies of PADI4 in rheumatoid arthritis. |
| title | Genetic and genomic studies of PADI4 in rheumatoid arthritis. |
| title_full | Genetic and genomic studies of PADI4 in rheumatoid arthritis. |
| title_fullStr | Genetic and genomic studies of PADI4 in rheumatoid arthritis. |
| title_full_unstemmed | Genetic and genomic studies of PADI4 in rheumatoid arthritis. |
| title_short | Genetic and genomic studies of PADI4 in rheumatoid arthritis. |
| title_sort | genetic and genomic studies of padi4 in rheumatoid arthritis |
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