Morphology and Progression in Primary Varicose Vein Disorder Due to 677C>T and 1298A>C Variants of MTHFR

•MTHFR polymorphism c.677C>T characterizes axial trunk and c.1298A>C perforator type morphology in primary varicose veins.•Mutant genotypes are associated with complicated phenotypes of the disease.•Genetic hint for distinct perforator type morphology associating further with congestive (CEAP C3–6) disease is provided.

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.