Prognostic role of factor XIII gene variants in nonhealing venous leg ulcers.
OBJECTIVE
Many factors impair healing of chronic venous ulcer (CVU), and many theories have been proposed to explain their pathogenesis. Coagulation factor XIII (FXIII) influences tissue regeneration and angiogenesis with effects on wound healing. Because FXIII properties depend upon its genetic variants, we investigated whether intragene polymorphisms may have modulating effects on the CVU area.


METHODS
The study included 121 patients with nonhealing CVUs (CEAP clinical class C6) that included 67% with primary chronic venous disease (CVD), 26% with post-thrombotic ulcers, and 7% with mixed ulcer origin. Polymerase chain reaction was used to genotype them for Val34Leu, Pro564Leu, and Tyr204Phe variants in the FXIII-A subunit gene and for His95Arg variant in the FXIII-B subunit gene. The same variants were analyzed in 102 controls, healthy subjects who were case-matched by age and gender.


RESULTS
Genotype distribution for all polymorphisms investigated was not significantly different between cases and controls. Conversely, our CVU cases had a mean ulcer area inversely related with the presence of both Leu34 and Leu564 alleles (ValVal, 12.3 +/- 22.4 cm2 vs LeuLeu, 3.9 +/- 2.6 cm2, P = .002; ProPro, 10.2 +/- 21.2 cm2 vs LeuLeu, 2.9 +/- 1.4 cm2, P = .002). In combined analysis, those cases who were wild-type for both variants (ValVal34/ProPro564) had a further increase in mean ulcer size compared with cases carrying both variants (Leu34/Leu564) (13.3 +/- 27.1 cm2 vs 5.2 +/- 5.6 cm2; P = .034).


CONCLUSIONS
No correlation exists between FXIII genotypes and the prevalence of chronic venous ulcers, thus demonstrating that FXIII polymorphisms have no role in ulcer development. In contrast, FXIII-gene variants, in particular the non-wild-type alleles Leu34 and Leu564, were associated with a smaller venous ulcer surface and might have favorable effects on reparative processes.
Tognazzo
Silvia
S
Center Study Haemostasis and Thrombosis, University of Ferrara, Ferrara, Italy.
Gemmati
Donato
D
Palazzo
Annunziata
A
Catozzi
Linda
L
Carandina
Sergio
S
Legnaro
Andrea
A
Tacconi
Giovanna
G
Scapoli
Gian L
GL
Zamboni
Paolo
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004247:DNA / Q000235:genetics*; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D012189:Retrospective Studies; D014647:Varicose Ulcer / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D014945:Wound Healing
C064015:factor XIII subunit A; D004247:DNA; D005176:Factor XIII; C054380:factor XIIIb