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131. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

25.03. - 28.03.2014, Berlin

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Genetic and epigenetic considerations in the pathogenesis of primary varicose veins and complicated disease

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  • Sotirios Katsandris - Johanniter-Krankenhaus Duisburg, Chirurgie I, Duisburg
  • Alexis Cooper - Universitätsmedizin Mainz, Institut für Humangenetik, Mainz
  • Nadine Glaser - Universitätsmedizin Mainz, Institut für Humangenetik, Mainz
  • Ulrich Zechner - Universitätsmedizin Mainz, Institut für Humangenetik, Mainz
  • Alexander Meyer - Johanniter-Krankenhaus Duisburg, Chirurgie I, Duisburg
  • Paul Karl Walter - Krankenhaus Maria Hilf GmbH, Abtl. für Gefäß- und Endovaskulare Chirurgie, Daun
  • Christoph Wilmanns - Johanniter-Krankenhaus Duisburg, Chirurgie I, Duisburg

Deutsche Gesellschaft für Chirurgie. 131. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 25.-28.03.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc14dgch547

doi: 10.3205/14dgch547, urn:nbn:de:0183-14dgch5472

Published: March 21, 2014

© 2014 Katsandris et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Introduction: Primary varicose vein disease constitutes a degenerative disorder with hereditary traits. Previous investigations suggested a correlation of the methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T and thrombophilic complications.

Material and methods: Age, gender, pedigree, and the MTHFR-polymorphisms C677T and A1298C, as well as patterns of methylation of the COL1A1 (collagen type 1, alpha 1) and FBN1 (Fibrillin 1) gene or the repetitive elements LINE1 and ALU, indicating genome wide methylation, were determined in blood and tissue of patients with uncomplicated (CEAP C2) and complicated varicose vein disease or negative controls. Congestive syndrome (CEAP C3-6), varicophlebitis, or recurrence were considered as complicated disease. Patients with peripheral occlusive arterial disease or carotidal stenosis served as negative controls.

Results: 131 patients entered the study so far. The age (number, median, range) of the first 60 patients was younger in uncomplicated (15, 56, [41;90]) or complicated (28, 59.5, [36;80]) disease compared to negative controls (17, 73, [47;89]). Women were more frequent in uncomplicated (8) or complicated (18) varicose vein disease, men in controls (15). Pedigrees of 66 patients evaluated suggest an autosomal-dominant pattern of inheritance (germ line mutation) in 1 out of 19 controls, 27 out of 31 uncomplicated, and 12 out of 16 complicated varicose veins and a sporadic occurrence in 4/4/4. Homocygoes polymorphisms of MTHFR T677T or C1298C (first 60 patients) were significantly more frequent in complicated (congestive syndrome: p<0.01, varicophlebitis: p<0.05, Pearson`s X2-Test) compared to uncomplicated disease or controls. While methylation of LINE1 and ALU elements or of the FBN1-gene was similar in blood and tissue, methylation of the COL1A1-gene was significantly higher only in tissue of varicophlebitis (11.9±4.3%) compared to uncomplicated disease (8.0±2.0%, p<0.003, Student`s t-test) or controls (7.0±1.3%), but not in blood.

Table 1 [Tab. 1]

Conclusion: The results suggest a hereditary origin of primary varicose vein disease and a contribution of genetic (MTHFR-polymorphisms C677T and A1298C) as well as of epigenetic (lower expression of COL1A1) mechanisms in the pathogenesis of complicated course of disease. The causal genetic defect of primary varicose vein disease, however, remains to be determined.