{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T19:10:27Z","timestamp":1772305827607,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Dupuytren\u2019s contracture (DC) represents a chronic fibroproliferative pathology of the palmar aponeurosis, which leads to flexion contractures of finger joints and hand disability. In recent decades, the WNT signaling pathway has been revealed to play a significant role in the manifestation and pathogenesis of DC. Our study aimed to evaluate the associations between Dupuytren\u2019s contracture and WNT-related single-nucleotide polymorphisms: Wnt Family Member 7B (WNT7B) rs6519955 (G\/T), Secreted Frizzled Related Protein 4 (SFRP4) rs17171229 (C\/T) and R-spondin 2 (RSPO2) rs611744 (A\/G). We enrolled 216 patients (113 DC cases and 103 healthy controls), and DNA samples were extracted from the peripheral blood. Genotyping of WNT7B rs6519955, SFRP4 rs17171229 and RSPO2 rs611744 was performed using the Real-Time PCR System 7900HT from Applied Biosystems. WNT7B rs6519955 genotype TT carriers were found to possess a higher prevalence of DC (OR = 3.516; CI = 1.624\u20137.610; p = 0.001), whereas RSPO2 rs611744 genotype GG appears to reduce the likelihood of the manifestation of DC nearly twofold (OR = 0.484, CI = 0.258\u20130.908, p = 0.024). In conclusion, SNPs WNT7B rs6519955 and RSPO2 rs611744 are associated with the development of Dupuytren\u2019s contracture: WNT7B rs6519955 TT genotype increases the chances by 3.5-fold, and RSPO2 rs611744 genotype GG appears to attenuate the likelihood of the manifestation of DC nearly twofold. Findings of genotype distributions among DC patients and control groups suggest that SFRP4 rs17171229 is not significantly associated with development of the disease.<\/jats:p>","DOI":"10.3390\/genes12091293","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T04:43:43Z","timestamp":1629780223000},"page":"1293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of WNT Signaling Pathway Gene Variants WNT7B rs6519955, SFRP4 rs17171229 and RSPO2 rs611744 in Patients with Dupuytren\u2019s Contracture"],"prefix":"10.3390","volume":"12","author":[{"given":"Gediminas","family":"Samul\u0117nas","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Lithuanian University of Health Sciences, LT 50009 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Smalinskien\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cardiology, Institute of Cardiology, Lithuanian University of Health Sciences, LT 50103 Kaunas, Lithuania"},{"name":"Institute of Biology Systems and Genetics Research, Lithuanian University of Health Sciences, LT 50103 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rytis","family":"Rimdeika","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Lithuanian University of Health Sciences, LT 50009 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u0119stutis","family":"Braziulis","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Lithuanian University of Health Sciences, LT 50009 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mantas","family":"Fomkinas","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Lithuanian University of Health Sciences, LT 50009 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rokas","family":"Pa\u0161kevi\u010dius","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lithuanian University of Health Sciences, LT 50009 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","first-page":"131","article-title":"Dupuytren\u2019s contracture: Fibroblast contraction? An ultrastructural study","volume":"66","author":"Gabbiani","year":"1972","journal-title":"Am. J. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.hcl.2018.03.001","article-title":"The basic science of Dupuytren disease","volume":"34","author":"Zhang","year":"2018","journal-title":"Hand Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s12079-016-0331-0","article-title":"Update on the role of molecular factors and fibroblasts in the pathogenesis of Dupuytren\u2019s disease","volume":"10","author":"Tripoli","year":"2016","journal-title":"J. Cell Commun. Signal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1056\/NEJMoa1101029","article-title":"Wnt signaling and Dupuytren\u2019s disease","volume":"365","author":"Dolmans","year":"2011","journal-title":"New Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Becker, K., Siegert, S., Toliat, M.R., Du, J., Casper, R., Dolmans, G.H., Werker, P.M., Tinschert, S., Franke, A., and Gieger, C. (2016). Meta-analysis of genome-wide association studies and network analysis-based integration with gene expression data identify new suggestive loci and unravel a wnt-centric network associated with Dupuytren\u2019s disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158101"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/cge.12410","article-title":"The importance of genetic susceptibility in Dupuytren\u2019s disease","volume":"87","author":"Becker","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.hcl.2018.03.002","article-title":"Risk Factors, Disease Associations, and Dupuytren Diathesis","volume":"34","author":"Hindocha","year":"2018","journal-title":"Hand Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s11552-010-9306-4","article-title":"Prevalence, incidence, and treatments of Dupuytren\u2019s disease in the United States: Results from a population-based study","volume":"6","author":"DiBenedetti","year":"2010","journal-title":"Hand"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1038\/modpathol.2010.146","article-title":"Unique microRNA profile in Dupuytren\u2019s contracture supports deregulation of \u03b2-catenin pathway","volume":"23","author":"Mosakhani","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.jhsa.2006.08.012","article-title":"Factors in the Pathogenesis of Dupuytren\u2019s Contracture","volume":"31","year":"2006","journal-title":"J. Hand Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1038\/sj.onc.1206415","article-title":"Beta-catenin expression in Dupuytren\u2019s disease: Potential role for cell\u2014matrix interactions in modulating beta-catenin levels in vivo and in vitro","volume":"22","author":"Varallo","year":"2003","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nrg1427","article-title":"WNT and \u03b2-catenin signalling: Diseases and therapies","volume":"5","author":"Moon","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1142\/S0218810414300058","article-title":"Dupuytren\u2019s contracture: Emerging insight into a viking disease","volume":"19","author":"Nunn","year":"2014","journal-title":"Hand Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1097\/PRS.0b013e3182442343","article-title":"DNA copy number variations at chromosome 7p14.1 and chromosome 14q11.2 are associated with Dupuytren\u2019s disease","volume":"129","author":"Shih","year":"2012","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3121\/cmr.2013.1199","article-title":"SNPs Previously associated with Dupuytren\u2019s disease replicated in a North American cohort","volume":"12","author":"Anderson","year":"2014","journal-title":"Clin. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.trsl.2015.09.006","article-title":"Wnt pathway in Dupuytren disease: Connecting profibrotic signals","volume":"166","author":"Dam","year":"2015","journal-title":"Transl. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s12079-015-0312-8","article-title":"Further evidence of the involvement of the Wnt signaling pathway in Dupuytren\u2019s disease","volume":"10","author":"Dam","year":"2016","journal-title":"J. Cell Commun. Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1111\/jcmm.13085","article-title":"Activation of Wnt\/\u03b2-catenin signalling is required for TGF-\u03b2\/Smad2\/3 signalling during myofibroblast proliferation","volume":"21","author":"Xu","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0007-1226(95)90029-2","article-title":"Epithelioid sarcoma masquerading as Dupuytren\u2019s disease","volume":"48","author":"Erdmann","year":"1995","journal-title":"Br. J. Plast. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2088","DOI":"10.1097\/GOX.0000000000002088","article-title":"Association between stenosing tenosynovitis and Dupuytren\u2019s contracture in the hand","volume":"7","author":"Yang","year":"2019","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1111\/jcmm.12856","article-title":"Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and epithelial-mesenchymal transition in triple-negative breast cancer","volume":"20","author":"Lv","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/onc.2016.304","article-title":"Wnt signaling in cancer","volume":"36","author":"Zhan","year":"2017","journal-title":"Oncogene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.ajhg.2017.08.006","article-title":"A genome-wide association study of Dupuytren disease reveals 17 additional variants implicated in fibrosis","volume":"101","author":"Ng","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1161\/CIRCRESAHA.110.219840","article-title":"An updated overview on Wnt signaling pathways","volume":"106","author":"Rao","year":"2010","journal-title":"Circ. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/0363-5023(88)90262-6","article-title":"Cigarette smoking and Dupuytren\u2019s contracture of the hand","volume":"13","author":"An","year":"1988","journal-title":"J. Hand Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1302\/0301-620X.79B2.0790206","article-title":"Smoking, alcohol and the risk of Dupuytren\u2019s contracture","volume":"79","author":"Burge","year":"1997","journal-title":"J. Bone Jt. Surgery. Br. Vol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e004214","DOI":"10.1136\/bmjopen-2013-004214","article-title":"Association among work exposure, alcohol intake, smoking and Dupuytren\u2019s disease in a large cohort study (GAZEL)","volume":"4","author":"Descatha","year":"2014","journal-title":"BMJ Open"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12920-019-0518-3","article-title":"Integrative genomic and transcriptomic analysis of genetic markers in Dupuytren\u2019s disease","volume":"12","author":"Jung","year":"2019","journal-title":"BMC Med. Genom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"964e","DOI":"10.1097\/01.prs.0000434410.40217.23","article-title":"Dupuytren disease","volume":"132","author":"Huisstede","year":"2013","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2217\/ijr.14.14","article-title":"Overview of the pathogenesis, diagnosis and treatment of Dupuytren\u2019s disease","volume":"9","author":"Mandel","year":"2014","journal-title":"Int. J. Clin. Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E928","DOI":"10.1073\/pnas.1301100110","article-title":"Unraveling the signaling pathways promoting fibrosis in Dupuytren\u2019s disease reveals TNF as a therapeutic target","volume":"110","author":"Verjee","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/9\/1293\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:50:13Z","timestamp":1760165413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/9\/1293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["genes12091293"],"URL":"https:\/\/doi.org\/10.3390\/genes12091293","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,24]]}}}