Search: WFRF:(Herrick A.) > (2010-2014) > A rare polymorphism...
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000 | 04266naa a2200553 4500 | |
001 | oai:lup.lub.lu.se:8d53e17a-1c1a-40b8-b08f-1da53588d85a | |
003 | SwePub | |
008 | 160401s2012 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/23550372 URI |
024 | 7 | a https://doi.org/10.1002/art.333252 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 Broen, J. C. A.4 aut |
245 | 1 0 | a A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators |
264 | c 2011-12-29 | |
264 | 1 | b Wiley,c 2012 |
520 | a Objective To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc). Methods. We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc patients and 537 controls and a replication cohort consisting of 1,170 SSc patients and 925 controls. In addition, we analyzed 15-year followup data on 964 patients to assess the potential association of TLR variants with the development of disease complications. We analyzed the functional impact of the associated polymorphism on monocyte-derived dendritic cells. Results. In the discovery cohort, we observed that a rare functional polymorphism in TLR2 (Pro631His) was associated with antitopoisomerase (antitopo) positivity (odds ratio 2.24 [95% confidence interval 1.24-4.04], P = 0.003). This observation was validated in the replication cohort (odds ratio 2.73 [95% confidence interval 1.85-4.04], P = 0.0001). In addition, in the replication cohort the TLR2 variant was associated with the diffuse subtype of the disease (P = 0.02) and with the development of pulmonary arterial hypertension (PAH) (Cox proportional hazards ratio 5.61 [95% confidence interval 1.53-20.58], P = 0.003 by log rank test). Functional analysis revealed that monocyte-derived dendritic cells carrying the Pro63His variant produced increased levels of inflammatory mediators (tumor necrosis factor alpha and interleukin-6) upon TLR-2-mediated stimulation (both P < 0.0001). Conclusion. Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated with antitopoisomerase positivity, the diffuse form of the disease, and the development of PAH. In addition, this variant influences TLR-2-mediated cell responses. Further research is needed to elucidate the precise role of TLR-2 in the pathogenesis of SSc. | |
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 Bossini-Castillo, L.4 aut |
700 | 1 | a van Bon, L.4 aut |
700 | 1 | a Vonk, M. C.4 aut |
700 | 1 | a Knaapen, H.4 aut |
700 | 1 | a Beretta, L.4 aut |
700 | 1 | a Rueda, B.4 aut |
700 | 1 | a Hesselstrand, Rogeru 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-rhe |
700 | 1 | a Herrick, A.4 aut |
700 | 1 | a Worthington, J.4 aut |
700 | 1 | a Hunzelman, N.4 aut |
700 | 1 | a Denton, C. P.4 aut |
700 | 1 | a Fonseca, C.4 aut |
700 | 1 | a Riemekasten, G.4 aut |
700 | 1 | a Kiener, H. P.4 aut |
700 | 1 | a Scorza, R.4 aut |
700 | 1 | a Simeon, C. P.4 aut |
700 | 1 | a Ortego-Centeno, N.4 aut |
700 | 1 | a Gonzalez-Gay, M. A.4 aut |
700 | 1 | a Airo, P.4 aut |
700 | 1 | a Coenen, M. J. H.4 aut |
700 | 1 | a Martin, J.4 aut |
700 | 1 | a Radstake, T. R. D. J.4 aut |
710 | 2 | a Reumatologi och molekylär skelettbiologib Sektion III4 org |
773 | 0 | t Arthritis and Rheumatismd : Wileyg 64:1, s. 264-271q 64:1<264-271x 1529-0131x 0004-3591 |
856 | 4 | u http://dx.doi.org/10.1002/art.33325y FULLTEXT |
856 | 4 8 | u https://lup.lub.lu.se/record/2355037 |
856 | 4 8 | u https://doi.org/10.1002/art.33325 |
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