Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension

Donato Gemmati, Silvia Tognazzo, Maria L. Serino, Luisella Fogato, Sergio Carandina, Massimiliano De Palma, Marcello Izzo, Monica De Mattei, Alessia Ongaro, Gian L. Scapoli, Angelo Caruso, Alberto Liboni, Paolo Zamboni

Research output: Contribution to journalArticle

Abstract

Low Factor XIII (FXIII) activity has been reported in the blood of patients with chronic venous leg ulcer (CVU). In vivo studies have described increased wound healing in CVU patients treated with FXIII concentrate, and in vitro studies have shown increased regenerative capacity in FXIII-treated fibroblasts. In addition, a common G-to-T polymorphism in the FXIIIA-subunit gene (V34L) significantly increases the activity and modifies the cross-linking properties of the FXIII molecule and this variant has been investigated as a protective factor against thrombosis, a recognized risk factor for CVU establishment. Therefore, the role of FXIII levels, FXIII V34L, FVR506Q, and FIIG20210A, common gene polymorphisms in the pathogenesis of CVU was investigated. Ninety-one patients with CVU and 195 healthy controls (91 of them sex- and age-matched) were PCR-genotyped for the FXIIIV34L, FVR506Q, and FIIG20210A substitutions and FXIIIA-subunit levels were determined by immuno-electrophoresis. The extent of the venous ulcer surface in patients was measured by computer software. The allele frequency and the genotype distribution of the FXIII polymorphism did not show significant differences between the whole group of cases and controls as well as prothrombin variants did. On the contrary, the FVR506Q variant (FV Leiden) allele was more frequent in patients, yielding a significant OR value of 5.93 (95 percent CI, 1.83-19.17; p = 0.003). Considering only CVU cases secondary to a post-thrombotic syndrome (n = 24), FV Leiden yielded a greater OR value of 16.08 (95 percent CI, 4.33-59.6; p <0.0001). When the CVU cases were stratified by the three possible FXIII genotypes, a significant trend toward a lower mean value of the ulcerated area was clearly evident as the number of the polymorphic alleles (L34) increased in the genotype of patients (VV = 11.9 cm2, ± 23.6; VL = 6.1 cm2, ± 6.9; LL = 4.1 cm2, ± 2.8; p = 0.01). On the other hand, FXIIIA antigen levels were similar between CVU cases and matched controls, but 11 percent of cases had FXIII deficiency (FXIIIA ≤ 0.65 U/ml; p = 0.003) and they showed a greater mean extension of the lesion if compared with the remaining cases without FXIIIA deficiency (14.5 cm2, ± 20.2 vs. 9.0 cm2, ± 6.3; p = 0.08). We conclude that FXIII antigen levels and FXIII V34L polymorphism may play a crucial role in the complex cascade of CVU pathophysiology, being significantly related to the CVU progression and extension because of the direct effects they have on the FXIII molecular activity.

Original languageEnglish
Pages (from-to)512-517
Number of pages6
JournalWound Repair and Regeneration
Volume12
Issue number5
DOIs
Publication statusPublished - Sep 2004

ASJC Scopus subject areas

  • Dermatology
  • Surgery

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    Gemmati, D., Tognazzo, S., Serino, M. L., Fogato, L., Carandina, S., De Palma, M., Izzo, M., De Mattei, M., Ongaro, A., Scapoli, G. L., Caruso, A., Liboni, A., & Zamboni, P. (2004). Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension. Wound Repair and Regeneration, 12(5), 512-517. https://doi.org/10.1111/j.1067-1927.2004.012503.x