Metalloproteinase gene expression correlates with clinical outcome in Dupuytren's disease.

Abstract

PURPOSE:

We have previously demonstrated that gene expression levels of matrix metalloproteinases (MMPs), related metalloproteinases "a disintegrin and metalloproteinase with thrombospontin motifs" (ADAMTSs), and tissue inhibitors of metalloproteinases (TIMPs) differed when comparing palmar fascia from 19 patients with Dupuytren's disease (DD) with 19 disease-free controls. We undertook to investigate whether the extent of this altered gene expression was related to clinical outcome.

METHODS:

All the patients with DD were followed up for an average of 14 months from their primary fasciectomy. Clinical outcome was scored by measuring range of motion to assess total extension deficit (fixed flexion deformity [FFD] of the affected digit), total further flexion, and grip strength, and using 3 validated outcome scores: the Disability of Arm, Shoulder and Hand (DASH) questionnaire, the Michigan Hand Questionnaire (MHQ), and the Vancouver Scar Scale (VSS).

RESULTS:

We found a considerable correlation between levels of gene expression of several of the MMPs (MMP2, MMP13, MMP14, MMP16, MMP 19) and ADAMTSs (ADAMTS2, ADAMTS4, ADAMTS5, ADAMTS14, ADAMTS16) and the recurrence of FFD over the follow-up period. The expression of all these genes had been shown to be increased in DD samples compared with controls. We also found that the expression levels of several of these genes correlated with 2 other preoperative measurements, total further flexion (digital roll-up) and grip strength.

CONCLUSIONS:

These findings suggest that gene expression levels of key MMPs and ADAMTSs could be used to predict 1-year clinical outcome in terms of recurrent FFD of the affected finger following fasciectomy for DD. This implies that knowledge of these expression levels could be used to direct appropriate surgical and adjuvant intervention for DD. This study also provides further evidence to support the functional link between metalloproteinase gene expression and symptomatic progression or recurrence.

TYPE OF STUDY/LEVEL OF EVIDENCE:

Prognostic IV.

• Authors: Phillip Johnston, Debbie Larson, Ian M Clark, Adrian J Chojnowski
• Journal: The Journal of hand surgery (J Hand Surg Am) Vol. 33 Issue 7 Pg. 1160-7 (Sep 2008) ISSN: 1531-6564 [Electronic] United States
• PMID: 18762113 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tissue Inhibitor of Metalloproteinases
• Metalloproteases
• ADAM Proteins
• Matrix Metalloproteinases

Topics

• ADAM Proteins (genetics)
• Adult
• Aged
• Aged, 80 and over
• Dupuytren Contracture (genetics, physiopathology, surgery)
• Female
• Gene Expression
• Humans
• Male
• Matrix Metalloproteinases (genetics)
• Metalloproteases (genetics)
• Middle Aged
• Tissue Inhibitor of Metalloproteinases (genetics)