Search: onr:"swepub:oai:lup.lub.lu.se:c0509b7b-adf5-4f18-84a2-de99cbdc9e98" > A genetic variant i...
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000 | 04672naa a2200481 4500 | |
001 | oai:lup.lub.lu.se:c0509b7b-adf5-4f18-84a2-de99cbdc9e98 | |
003 | SwePub | |
008 | 160401s2014 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/50915032 URI |
024 | 7 | a https://doi.org/10.1186/ar45582 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Knevel, Rachel4 aut |
245 | 1 0 | a A genetic variant in osteoprotegerin is associated with progression of joint destruction in rheumatoid arthritis |
264 | 1 | b Springer Science and Business Media LLC,c 2014 |
338 | a electronic2 rdacarrier | |
520 | a Introduction: Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor kappa B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA. Methods: 1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied. Results: We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P = 2.35x10(-4)). This variant was also significant after Bonferroni correction. Conclusions: These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reumatologi och inflammation0 (SwePub)302102 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Rheumatology and Autoimmunity0 (SwePub)302102 hsv//eng |
700 | 1 | a de Rooy, Diederik P. C.4 aut |
700 | 1 | a Saxne, Toreu Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)reum-tsa |
700 | 1 | a Lindqvist, Elisabetu Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)reum-eli |
700 | 1 | a Leijsma, Martha K.4 aut |
700 | 1 | a Daha, Nina A.4 aut |
700 | 1 | a Koeleman, Bobby P. C.4 aut |
700 | 1 | a Tsonaka, Roula4 aut |
700 | 1 | a Houwing-Duistermaat, Jeanine J.4 aut |
700 | 1 | a Schonkeren, Joris J. M.4 aut |
700 | 1 | a Toes, Rene E. M.4 aut |
700 | 1 | a Huizinga, Tom W. J.4 aut |
700 | 1 | a Brouwer, Elisabeth4 aut |
700 | 1 | a Wilson, Anthony G.4 aut |
700 | 1 | a van der Helm-van Mil, Annette H. M.4 aut |
710 | 2 | a Reumatologi och molekylär skelettbiologib Sektion III4 org |
773 | 0 | t Arthritis Research and Therapyd : Springer Science and Business Media LLCg 16:3q 16:3x 1478-6362x 1478-6354 |
856 | 4 | u https://portal.research.lu.se/files/2184804/7761643x primaryx freey FULLTEXT |
856 | 4 | u http://dx.doi.org/10.1186/ar4558x freey FULLTEXT |
856 | 4 | u https://arthritis-research.biomedcentral.com/track/pdf/10.1186/ar4558 |
856 | 4 8 | u https://lup.lub.lu.se/record/5091503 |
856 | 4 8 | u https://doi.org/10.1186/ar4558 |
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