{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:02:30Z","timestamp":1791291750050,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"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>(1) Background: genetic variations, localized in the functional regions of the extracellular matrix (ECM) modulation-related genes, may alter the transcription process and impact the Dupuytren\u2019s contracture (DC). The present study investigated the association of single nucleotide polymorphisms (SNPs), localized in the functional regions of the MMP8, MMP14, and CHST6 genes, with DC risk. (2) Methods: we enrolled 219 genomic DNA samples, which were extracted from 116 patients with DC and 103 healthy controls. Genotyping of selected SNPs was performed using TaqMan single nucleotide polymorphisms genotyping assay. Three polymorphisms (MMP8 rs11225395, MMP14 rs1042704, and CHST6 rs977987) were analyzed. All studied SNPs were in Hardy\u2013Weinberg equilibrium. (3) Results: significant associations of the studied SNPs with the previous onset of the disease were observed between the CHST6 rs977987 minor T allele (p = 0.036) and the MMP14 rs1042704 mutant AA genotype (p = 0.024). Significant associations with the previous onset of the disease were also observed with a positive family history of the DC (p = 0.035). Moreover, risk factor analysis revealed that a combination of major disease risk factors (smoking and manual labor) and the MMP14 minor A allele increases the risk of DC development by fourteen times (p = 0.010). (4) Conclusions: our findings suggest that CHST6 rs977987, MMP14 rs1042704, and positive family history are associated with the previous onset of Dupuytren\u2019s contracture. In addition, the combination of the MMP14 minor A allele and additional risk factors increase the likelihood of the manifestation of the DC.<\/jats:p>","DOI":"10.3390\/genes13050743","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T08:14:06Z","timestamp":1650701646000},"page":"743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Role of Functional Polymorphisms in the Extracellular Matrix Modulation-Related Genes on Dupuytren\u2019s Contracture"],"prefix":"10.3390","volume":"13","author":[{"given":"Gediminas","family":"Samulenas","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Lithuanian University of Health Sciences, LT 50009 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruta","family":"Insodaite","sequence":"additional","affiliation":[{"name":"Institute of Biology Systems and Genetics Research, Lithuanian University of Health Sciences, LT 50103 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edita","family":"Kunceviciene","sequence":"additional","affiliation":[{"name":"Institute of Biology Systems and Genetics Research, Lithuanian University of Health Sciences, LT 50103 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Poceviciute","sequence":"additional","affiliation":[{"name":"Institute of Biology Systems and Genetics Research, Lithuanian University of Health Sciences, LT 50103 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Masionyte","sequence":"additional","affiliation":[{"name":"Institute of Biology Systems and Genetics Research, Lithuanian University of Health Sciences, LT 50103 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urte","family":"Zitkeviciute","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreta","family":"Pilipaityte","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Lithuanian University of Health Sciences, LT 50009 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Smalinskiene","sequence":"additional","affiliation":[{"name":"Institute of Biology Systems and Genetics Research, Lithuanian University of Health Sciences, LT 50103 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,23]]},"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":"10.1016\/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_5","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":"2011","journal-title":"Hand"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1097\/PRS.0b013e3182958a33","article-title":"Prevalence of Dupuytren Disease in the Netherlands","volume":"132","author":"Lanting","year":"2013","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_7","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_8","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_9","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":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"635","DOI":"10.2106\/00004623-195941040-00008","article-title":"Dupuytren\u2019s Contracture; a New Concept of the Pathogenesis Correlated with Surgical Management","volume":"41-A","author":"Luck","year":"1959","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13069-016-0046-0","article-title":"Matrix and Cell Phenotype Differences in Dupuytren\u2019s Disease","volume":"9","author":"Werker","year":"2016","journal-title":"Fibrogenes. Tissue Repair"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1007\/s00402-008-0726-3","article-title":"Expression of Matrix Metalloproteinases and Their Inhibitors in Cords and Nodules of Patients with Dupuytren\u2019s Disease","volume":"129","author":"Ulrich","year":"2009","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1016\/j.bmc.2007.01.011","article-title":"Matrix Metalloproteinases (MMPs): Chemical-Biological Functions and (Q)SARs","volume":"15","author":"Verma","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4103\/0973-1482.157337","article-title":"Seesaw of Matrix Metalloproteinases (MMPs)","volume":"12","author":"Kapoor","year":"2016","journal-title":"J. Cancer Res. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.bbadis.2012.02.001","article-title":"MMP-14 and MMP-2 Are Key Metalloproteases in Dupuytren\u2019s Disease Fibroblast-Mediated Contraction","volume":"1822","author":"Wilkinson","year":"2012","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3109\/03008207.2012.686542","article-title":"Expression of MMP-2, TIMP-2, TGF-\u03921, and Decorin in Dupuytren\u2019s Contracture","volume":"53","author":"Gosk","year":"2012","journal-title":"Connect. Tissue Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jhsa.2006.12.010","article-title":"A Complete Expression Profile of Matrix-Degrading Metalloproteinases in Dupuytren\u2019s Disease","volume":"32","author":"Johnston","year":"2007","journal-title":"J. Hand Surg. Am."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.apjtb.2016.07.017","article-title":"Therapeutic Applications of Collagenase (Metalloproteases): A Review","volume":"6","author":"Alipour","year":"2016","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2217\/ijr.11.4","article-title":"Collagenase Clostridium Histolyticum: A Novel Nonoperative Treatment for Dupuytren\u2019s Disease","volume":"6","author":"Watt","year":"2011","journal-title":"Int. J. Clin. Rheumtol."},{"key":"ref_20","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. Am."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/jnc.14652","article-title":"Keratan Sulfate (KS)-Proteoglycans and Neuronal Regulation in Health and Disease: The Importance of KS-Glycodynamics and Interactive Capability with Neuroregulatory Ligands","volume":"149","author":"Melrose","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1631\/jzus.B1100011","article-title":"Pathogenic Mutations of TGFBI and CHST6 Genes in Chinese Patients with Avellino, Lattice, and Macular Corneal Dystrophies","volume":"12","author":"Huo","year":"2011","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.matbio.2021.02.003","article-title":"A Common SNP Risk Variant MT1-MMP Causative for Dupuytren\u2019s Disease Has a Specific Defect in Collagenolytic Activity","volume":"97","author":"Itoh","year":"2021","journal-title":"Matrix Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19618","DOI":"10.18632\/aging.103930","article-title":"Matrix Metalloproteinase-8 Rs11225395 Polymorphism Correlates with Colorectal Cancer Risk and Survival in a Chinese Han Population: A Case-Control Study","volume":"12","author":"Tai","year":"2020","journal-title":"Aging (Albany. NY)."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Feng, J., Chen, Y., Hua, W., Sun, X., Chen, Y., Liu, Y., Fan, J., Zhao, Y., Zhao, L., and Xu, X. (2019). The MMP-8 Rs11225395 Promoter Polymorphism Increases Cancer Risk of Non-Asian Populations: Evidence from a Meta-Analysis. Biomolecules, 9.","DOI":"10.3390\/biom9100570"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5953","DOI":"10.1007\/s11033-013-2704-2","article-title":"Impact of Matrix Metalloproteinase-8 Gene Variations on the Risk of Thoracic Aortic Dissection in a Chinese Han Population","volume":"40","author":"Wang","year":"2013","journal-title":"Mol. Biol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: The NCBI database of genetic variation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7791","DOI":"10.4049\/jimmunol.172.12.7791","article-title":"Membrane-Bound Matrix Metalloproteinase-8 on Activated Polymorphonuclear Cells Is a Potent, Tissue Inhibitor of Metalloproteinase-Resistant Collagenase and Serpinase","volume":"172","author":"Owen","year":"2004","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.4049\/jimmunol.175.4.2589","article-title":"Matrix Metalloproteinase-8 Deficiency Promotes Granulocytic Allergen-Induced Airway Inflammation","volume":"175","author":"Gueders","year":"2005","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8635158","DOI":"10.1155\/2020\/8635158","article-title":"The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs)","volume":"2020","author":"Cancemi","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5435\/00124635-199801000-00003","article-title":"Dupuytren\u2019s Contracture","volume":"6","author":"Benson","year":"1998","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_32","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. Am."},{"key":"ref_33","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. Surg. Br."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/J.JHSE.2005.02.002","article-title":"An Assessment of the Effects of Exposure to Vibration, Smoking, Alcohol and Diabetes on the Prevalence of Dupuytren\u2019s Disease in 97,537 Miners","volume":"32","author":"Burke","year":"2007","journal-title":"J. Hand Surg. Eur. Vol."},{"key":"ref_35","first-page":"66","article-title":"Manual labor and Dupuytren disease. The results of a computerized survey in the field of iron metallurgy","volume":"2","author":"Wagner","year":"1983","journal-title":"Ann. Chir. Main Organe Off. Soc. Chir. Main"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1038\/s41431-019-0483-5","article-title":"Ethnic Differences in Prevalence of Dupuytren Disease Can Partly Be Explained by Known Genetic Risk Variants","volume":"27","author":"Riesmeijer","year":"2019","journal-title":"Eur. J. Hum. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/743\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:59:30Z","timestamp":1760137170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,23]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["genes13050743"],"URL":"https:\/\/doi.org\/10.3390\/genes13050743","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,23]]}}}