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Wnt signaling and Dupuytren's disease

Dolmans, G.H., Werker, P.M., Hennies, Hans C., Furniss, D., Festen, E.A., Franke, L., Becker, K., van der Vlies, P., Wolffenbuttel, B.H., Tinschert, S., Toliat, M.R., Nothnagel, M., Franke, A., Klopp, N., Wichmann, H.E., Nürnberg, P., Giele, H., Ophoff, R.A. and Wijmenga, C. (2011) Wnt signaling and Dupuytren's disease. New England Journal of Medicine, 365 (4). pp. 307-317. ISSN 0028-4793

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Abstract

BACKGROUND
Dupuytren's disease is a benign fibromatosis of the hands and fingers that leads to flexion contractures. We hypothesized that multiple genetic and environmental factors influence susceptibility to this disease and sought to identify susceptibility genes to better understand its pathogenesis.
METHODS
We conducted a genomewide association study of 960 Dutch persons with Dupuytren's disease and 3117 controls (the discovery set) to test for association between the disease and genetic markers. We tested the 35 single-nucleotide polymorphisms (SNPs) most strongly associated with Dupuytren's disease (P<1×10−4) in the discovery set in three additional, independent case series comprising a total of 1365 affected persons and 8445 controls from Germany, the United Kingdom, and the Netherlands.
RESULTS
Initially, we observed a significant genomewide association between Dupuytren's disease and 8 SNPs at three loci. Tests of replication and joint analysis of all data from 2325 patients with Dupuytren's disease and 11,562 controls yielded an association with 11 SNPs from nine different loci (P<5.0×10−8). Six of these loci contain genes known to be involved in the Wnt-signaling pathway: WNT4 (rs7524102) (P=2.8×10−9; odds ratio, 1.28), SFRP4 (rs16879765) (P=5.6×10−39; odds ratio, 1.98), WNT2 (rs4730775) (P=3.0×10−8; odds ratio, 0.83), RSPO2 (rs611744) (P=7.9×10−15; odds ratio, 0.75), SULF1 (rs2912522) (P=2.0×10−13; odds ratio, 0.72), and WNT7B (rs6519955) (P=3.2×10−33; odds ratio, 1.54).
CONCLUSIONS
This study implicates nine different loci involved in genetic susceptibility to Dupuytren's disease. The fact that six of these nine loci harbor genes encoding proteins in the Wnt-signaling pathway suggests that aberrations in this pathway are key to the process of fibromatosis in Dupuytren's disease.

Item Type: Article
Additional Information: Unmapped bibliographic data: ST - Wnt signaling and Dupuytren's disease [Field not mapped to EPrints] LB - 83 [Field not mapped to EPrints] RP - Not in File [Field not mapped to EPrints]
Uncontrolled Keywords: analysis
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Schools: School of Applied Sciences
Related URLs:
Depositing User: Hans Hennies
Date Deposited: 11 Jul 2016 14:41
Last Modified: 29 Jul 2016 13:16
URI: http://eprints.hud.ac.uk/id/eprint/28783

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