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A genetic variant i...
A genetic variant in granzyme B is associated with progression of joint destruction in rheumatoid arthritis
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Knevel, R. (author)
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Krabben, A. (author)
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Wilson, A. G. (author)
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Brouwer, E. (author)
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Leijsma, M. K. (author)
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- Lindqvist, Elisabet (author)
- 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 Medicine
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de Rooy, D. P. C. (author)
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Daha, N. A. (author)
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van der Linden, M. P. M. (author)
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Tsonaka, S. (author)
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Zhernakova, A. (author)
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Westra, H. -J. (author)
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Franke, L. (author)
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Houwing-Duistermaat, J. J. (author)
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Toes, R. E. M. (author)
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Huizinga, T. W. J. (author)
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- Saxne, Tore (author)
- 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 Medicine
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van der Helm-van Mil, A. H. M. (author)
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(creator_code:org_t)
- 2013-02-25
- 2013
- English.
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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 65:3, s. 582-589
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Abstract
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- Objective Genetic factors account for an estimated 4558% of the variance in joint destruction in rheumatoid arthritis (RA). The serine proteinase granzyme B induces target cell apoptosis, and several in vitro studies suggest that granzyme B is involved in apoptosis of chondrocytes. Serum levels of granzyme B are increased in RA and are also associated with radiographic erosions. The aim of this study was to investigate GZMB as a candidate gene accounting for the severity of joint destruction in RA. Methods A total of 1,418 patients with 4,885 radiograph sets of the hands and feet from 4 independent cohorts were studied. First, explorative analyses were performed in 600 RA patients in the Leiden Early Arthritis Clinic cohort. Fifteen single-nucleotide polymorphisms (SNPs) tagging GZMB were tested. Significantly associated SNPs were genotyped in data sets representing patients from the Groningen, Sheffield, and Lund cohorts. In each data set, the relative increase in the annual rate of progression in the presence of a genotype was assessed. Data were summarized in a meta-analysis. The association of GZMB with the RNA expression level of the GZMB genomic region was tested by mapping expression quantitative trait loci (QTLs) on 1,469 whole blood samples. Results SNP rs8192916 was significantly associated with the rate of joint destruction in the first cohort and in the meta-analysis of all data sets. Patients homozygous for the minor allele of rs8192916 had a higher rate of joint destruction per year compared with other patients (P = 7.8 x 104). Expression QTL of GZMB identified higher expression in the presence of the minor allele of rs8192916 (P = 2.27 x 105). Conclusion SNP rs8192916 located in GZMB is associated with the progression of joint destruction in RA as well as with RNA expression in whole blood.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Knevel, R.
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Krabben, A.
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Wilson, A. G.
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Brouwer, E.
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Leijsma, M. K.
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Lindqvist, Elisa ...
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show more...
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de Rooy, D. P. C ...
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Daha, N. A.
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van der Linden, ...
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Tsonaka, S.
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Zhernakova, A.
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Westra, H. -J.
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Franke, L.
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Houwing-Duisterm ...
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Toes, R. E. M.
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Huizinga, T. W. ...
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Saxne, Tore
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van der Helm-van ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
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Arthritis and Rh ...
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Lund University