Genetic susceptibility to keloid disease: Mutation screening of the TGFβ3 gene

Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and its presence in identical twins suggest a strong genetic predisposition to keloid formation. Transforming growth factor beta isoforms (TGFβ) play a central role in wound healing and fibrosis and have been implicated in KD pathogenesis. Recent data has suggested that TGFβ3 has an important role in scar formation. There is little known about the genetic variation present within the TGFβ3 gene, which contains seven exons and six introns spanning 43 000 base pairs of the human genome. Exons one to seven and the promoter region (1000 bp upstream from exon 1 in the 5′-flanking regions) were screened in 95 Caucasian KD cases and 95 Caucasian controls for the presence of novel mutations using a high throughput DHPLC mutation detection technology. There were no mutations identified in any of the exonic regions, however, multiple nondisease associated mutations were found in the promoter region of the TGFβ3 gene. These data demonstrate that there is no association between the exonic and promoter regions of TGFβ3 gene and keloid scarring in our cohort of Caucasian patients. © 2005 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.