BackgroundClinical assessment and prognostic stratification of primary varicose veins have remained controversial and the molecular pathogenesis is unknown. Previous data have suggested a contribution of the MTHFR (methylenetetrahydrofolate reductase) polymorphism c.677C>T.MethodsWe collected blood and vein specimens from 159 consecutive patients undergoing varicose vein surgery, or autologous vein reconstruction for arterial occlusive disease as controls. We compared the frequencies of c.677C>T and another polymorphism of MTHFR, c.1298A>C, with morphology and types of complicated disease. Morphology was recorded as a trunk or perforator type and peripheral congestive complication was defined as chronic venous insufficiency (CEAP C3–6) associated with edema and skin manifestations.FindingsMultivariate analysis of genotypes for c.677C>T and c.1298A>C indicated that c.677C>T was associated significantly with the trunk phenotype (43/53 patients, 81%, p < 0.01), while c.1298A>C was associated significantly with the perforator phenotype (18/24 patients, 75%, p < 0.01) of primary varicose veins. Accordingly, when both c.677C>T and c.1298A>C displayed a heterozygous genotype, the patients were more likely to present with both phenotypes. Additionally, c.1298A>C was found to be strongly linked to the congestive complication (34/51 patients, 67%, p < 0.01).InterpretationBoth polymorphisms of MTHFR may be involved in the morphological specification of primary varicose veins and contribute to the development of complicated disease.FundingNone.

(–) 15-Deoxyspergualin, originally discovered as an antitumoral drug, was shown to have different immunosuppressive effects, when pancreas and orthotopic allogeneic liver transplantations in rats were compared. In the strong rejection model dark agouti → Lewis (RTl^a → RT1¹) we could only show a minor immunosuppressive effect, as far as pancreaticoduodenal and pancreas segment transplantations are concerned: graft survival was prolonged by 9 days in pancreas segment allografts (p < 0.01) and by 6 days in pancreaticoduodenal allografts (p < 0.01), when recipients were treated by ten doses of 2.5 mg/kg deoxyspergualin. Pretreatment of recipients with 15-deoxyspergualin was not efficient. On the contrary, in orthotopic liver transplantation done by the cuff technique, a remarkable prolongation of allograft survival could be demonstrated: about half of the animals showed prolongation of allograft survival for more than 80 days, compared with about 11 days in the control group (p < 0.01). The substance is considered to be valuable for clinical application.

Factor V (FV)-Leiden (G16891A)-, factor II(G20210A)-mutations, protein C- and S, as well as methylenetetrahydrofolate reductase (MTHFR) polymorphisms at C677T and A1298C, and serum homocysteine levels (hcy) were determined in 29 patients with SVT and 26 with DVT. Findings FV- and -II-mutations were less frequent in patients with SVT (2/3) compared with DVT (9/5), respectively (P < 0.002 in case of FV). However, the frequency of the MTHFR C677T polymorphism was significantly higher in patients with SVT compared with DVT (CT 12 versus 10, and TT 7 versus 1, respectively, P << 0.001). The distribution of the MTHFR A1298C genotype and serum hcy levels was similar in both patient groups. Protein S-deficiency was recorded once (SVT). Interpretation These results suggest that the MTHFR C677T-mutant genetically predisposes its carriers to SVT which may contribute to hypercoagulation in pre-existing varicose vein disease.

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