title: Influence of gene polymorphisms in ulcer healing process after superficial venous surgery.
abstract: OBJECTIVE
  Role of superficial venous surgery in reducing the time it takes for ulcers to heal is still controversial, although all studies confirm a significant reduction in ulcer recurrences. Recently, the HFE-C282Y and FXIII-V34L gene variants demonstrated a role in the risk of venous ulceration in primary chronic venous disorder (CVD) and in modulating lesion size in chronic venous ulcer (CVU), respectively. This study was conducted to investigate the role of HFE-C282Y and FXIII (V34L and P564L) gene variants in ulcer healing time after superficial venous surgery, by assessing the outcome of a cohort of homogeneous CVU patients.
  
  
  METHODS
  The study selected 91 patients affected by primary CVU (CEAP C6, Ep, Asp, Pr), with the exclusion of any other comorbidity factor involved in delayed healing process, who underwent surgery. We assessed the ulcer area and the healing time. Patients were genotyped by polymerase chain reaction for FXIII (V34L and P564L) and for HFE-C282Y substitutions.
  
  
  RESULTS
  Globally, CVU cases had a postoperative mean healing time of 8.5 +/- 5.7 weeks. For the subset of cases above and below the median value (M = 8.0 weeks), FXIII-V34L genotype distribution significantly differed (P < .0001). In addition, Kaplan-Meier analysis yielded specific healing time profiles for the different FXIII-V34L classes of genotype (P = .00001), with an increased risk of delayed healing for the FXIII-VV genotype (hazard ratio, 4.14; 95% confidence interval, 2.1 to 8.2; P = .00005). Although FXIII-P54L genotype distributions did not differ, homozygous 564LL cases (P = .005) and double carriers for both FXIII variants (P < .0001), had a significantly reduced healing time vs wild types. No differences in healing time were observed between carriers and noncarriers of the HFE-C282Y variant, whereas when these cases were stratified by FXIII-V34L genotypes, the L34 carriers had a significantly shorter healing time, irrespective of the HFE genotype.
  
  
  CONCLUSIONS
  The FXIII-34L variant was significantly associated with shorter healing time after superficial venous surgery, suggesting a role in the healing and tissue regeneration phases. Conversely, HFE-C282Y, despite its role in ulcer establishment, did not affect the postoperative healing time. In perspective, the identification of patients with a poor prognosis may give clinicians the opportunity to modify management and to target tailored therapies in the view of a new and alternative concept of treatment based on pharmacogenomics.
authors.affiliation: Center Study Hemostasis and Thrombosis, University of Ferrara, Ferrara, Italy. d.gemmati@unife.it
authors.forename: Donato
authors.initials: D
authors.lastname: Gemmati
authors.forename: Silvia
authors.initials: S
authors.lastname: Tognazzo
authors.forename: Linda
authors.initials: L
authors.lastname: Catozzi
authors.forename: Federica
authors.initials: F
authors.lastname: Federici
authors.forename: Massimiliano
authors.initials: M
authors.lastname: De Palma
authors.forename: Sergio
authors.initials: S
authors.lastname: Gianesini
authors.forename: Gian L
authors.initials: GL
authors.lastname: Scapoli
authors.forename: Monica
authors.initials: M
authors.lastname: De Mattei
authors.forename: Alberto
authors.initials: A
authors.lastname: Liboni
authors.forename: Paolo
authors.initials: P
authors.lastname: Zamboni
mesh_terms: D000368:Aged; D005176:Factor XIII / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010991:Plethysmography; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D014647:Varicose Ulcer / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery*; D014945:Wound Healing / Q000235:genetics*
chemical_list: D005176:Factor XIII