Gemmati Donato, Tognazzo Silvia, Catozzi Linda, Federici Federica, De Palma Massimiliano, Gianesini Sergio, Scapoli Gian L, De Mattei Monica, Liboni Alberto, Zamboni Paolo
Center Study Hemostasis and Thrombosis, University of Ferrara, Ferrara, Italy.
J Vasc Surg. 2006 Sep;44(3):554-62. doi: 10.1016/j.jvs.2006.05.011.
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.
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.
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.
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.
尽管所有研究均证实浅静脉手术能显著降低溃疡复发率，但该手术在缩短溃疡愈合时间方面的作用仍存在争议。最近，HFE-C282Y和FXIII-V34L基因变异分别在原发性慢性静脉疾病（CVD）的静脉溃疡风险及慢性静脉溃疡（CVU）的病变大小调节中发挥作用。本研究旨在通过评估一组同质CVU患者的手术结果，探讨HFE-C282Y和FXIII（V34L和P564L）基因变异在浅静脉手术后溃疡愈合时间中的作用。
本研究选取了91例原发性CVU（CEAP C6，Ep，Asp，Pr）患者，排除了任何参与延迟愈合过程的其他合并症因素，这些患者均接受了手术。我们评估了溃疡面积和愈合时间。通过聚合酶链反应对患者进行FXIII（V34L和P564L）及HFE-C282Y替代基因分型。
总体而言，CVU患者术后平均愈合时间为8.5±5.7周。对于中位数（M = 8.0周）以上和以下的病例子集，FXIII-V34L基因型分布存在显著差异（P <.0001）。此外，Kaplan-Meier分析得出了不同FXIII-V34L基因型类别的特定愈合时间曲线（P =.00001），FXIII-VV基因型延迟愈合风险增加（风险比，4.14；95%置信区间，2.1至8.2；P =.00005）。尽管FXIII-P54L基因型分布无差异，但纯合564LL病例（P =.005）和两种FXIII变异的双重携带者（P <.0001）与野生型相比，愈合时间显著缩短。HFE-C282Y变异携带者与非携带者之间在愈合时间上未观察到差异，然而，当这些病例按FXIII-V34L基因型分层时，无论HFE基因型如何，L34携带者的愈合时间均显著缩短。
FXIII-34L变异与浅静脉手术后较短的愈合时间显著相关，表明其在愈合和组织再生阶段发挥作用。相反，HFE-C282Y尽管在溃疡形成中起作用，但不影响术后愈合时间。从长远来看，识别预后不良的患者可能使临床医生有机会调整治疗方案，并根据基于药物基因组学的新的替代治疗概念进行靶向个体化治疗。
