Dupuytren diathesis and genetic risk

Abstract

Purpose: Dupuytren disease (DD) is a benign fibrosing disorder of the hand and fingers. Recently, we identified 9 single nucleotide polymorphisms (SNPs) associated with DD in a genome-wide association study. These SNPs can be used to calculate a genetic risk score for DD. The aim of this study was to test whether certain clinical characteristics (including the DD diathesis features) of patients with DD are associated with a high genetic risk score.

Methods: Between 2007 and 2010, we prospectively invited all DD patients (1,120 in total) to participate. Clinical characteristics were noted using patient- and doctor-completed questionnaires, and blood was obtained for DNA analysis. We analyzed a total of 933 subjects with genetic and clinical data. The 9 previously identified DD SNPs were used to calculate a weighted genetic risk score. Patients were categorized into high and low genetic risk score groups, according to their weighted genetic risk score. Logistic regression was performed to study the association of clinical characteristics with a high genetic risk score.

Results: In a univariate regression model, patients with an age of onset of DD younger than 50 years, a family history positive for DD, knuckle pads, and Ledderhose disease were statistically significantly associated with a high genetic risk score. In an additional analysis using high and low genetic risk groups that deviate further from the median, Ledderhose disease was no longer significantly associated with DD.

Conclusions: Patients with DD who present with these diathesis features, and predominantly patients with knuckle pads, are more likely to carry more risk alleles for the discovered DD SNPs than patients without these diathesis features.

Clinical relevance: These markers may prove useful in predicting disease progression or recurrence.