Genetic Background of Venous Leg Ulcer Development

Abstract

Fibroblast growth factor receptor 2 gene codes for IIIb and IIIc transcript variants, which play pivotal roles in normal wound healing. Tumor necrosis factor α mediates several biological processes including wound healing. We aimed to characterise the expression pattern of IIIb expressed by in vitro cultured keratinocytes and in skin biopsy samples of venous leg ulcer patients, and to identify polymorphisms which may play a role in the pathomechanism of prolonged wound healing in venous leg ulcer patients. Real-time reverse transcription polymerase chain reaction and Western blotting methods were used for expression studies, polymerase chain reaction with TaqMan probes and with restriction fragment length polymorphism method were performed for polymorphism studies. We demonstrated that the expression of IIIb is related to the proliferation states of HaCaT keratinocytes and its expression is down-regulated in the uninvolved epidermis of venous leg ulcer patients ( n = 15) compared to the epidermis of controls ( n = 15). We identified a polymorphism in the 3’ untranslated region (2451A/G) of the fibroblast growth factor receptor 2 gene, which displayed a significant difference in the allelic distribution between leg ulcer patients ( n = 82) and controls ( n = 82; p = 0.0103). We hypothesize that this polymorphism may be a susceptibility factor for venous leg ulcer. In another set of experiment we demonstrated that the A allele of the –308 tumor necrosis factor α polymorphism might be a potential factor for venous leg ulcer susceptibility; however, our data suggest that this association is secondary and the primary association probably exists with obesity.