Dupuytren's Disease remains a puzzling challenge to hand surgeons since its first descriptions in the literature over 150 years ago. Although much is now understood about the behavior of the disease, general treatment principles, risk factors, outcomes, and the true underlying cause has remained elusive. The familial predisposition of Northern European Caucasians, the increased incidence amongst affected twins, and other associations have suggested a genetic predisposition to the development and expression of the disease. This study attempted to identify a possible genetic marker associated with the disease in susceptible individuals. Because of the known influence of TGF-B on the activity of myofibroblasts, the active cell type in contractile Dupuytren's cords, the authors directed their investigation to the expression of Zf9. Zf9 is a nuclear binding protein that has been found to induce fibrogenesis. It is thought to enhance the effect of TGF-B in vivo. Zf9 polymorphisms were examined in a group of patients with advanced Dupuytren's disease and normal controls. The study group of 138 patients (119 men, 19 women) were unrelated Caucasians between the ages of 25-90 with advanced Dupuytren's contractures. The control of 200 men and 55 women were ethnically matched healthy volunteers from 19-70 years of age. Zf9 polymorphism was evaluated by comparing the distribution of allele frequencies between Dupuytren's patients and controls. The study results revealed a statistically significant difference in allele frequencies between the two groups at the 3' untranslated region single nucleotide polymorphisms in the Zf9 gene. The G allele was associated with a significantly increased risk of developing Dupuytren's disease, as opposed to the A allele.
This study represents the first investigation to identify a genetic marker associated with the pathogenetic role of TGF-B in Dupuytren's disease. It confirms clinical observations of the likelihood of a genetic predisposition, and it strongly supports the earlier experimental work identifying TGF-B as an active biologic mediator of Dupuytren's contracture. It is therefore and extremely important step in the understanding of the cause of Dupuytren's disease and the pathogenesis of Dupuytren's contractures. It may help to identify at-risk populations and direct future gene therapies aimed at more effective treatment of this disabling disease.
Plastic & Reconstructive Surgery 111: 2133-2139, 2003.