Chronic Venous Disease Genetics

Prepared by Joseph Raffetto, MD

Corresponding chapter in Handbook of Venous Disorders: Chapters 6 and 9

• Cornu-Thenard A, Boivin P, Baud JM, DeVincenzi I, Carpentier PH. Importance of the familial factor in varicose disease. Clinical study of 134 families. J Dermatol Surg Oncol 1994;20:318-26.

PMID: 8176043

Comment: This case control study was an important study demonstrating a genetic basis for varicose veins. The hereditary basis
has autosomal dominant with variable penetrance; however the genetic basis for varicose veins is unknown.

• Zamboni P, Tognazzo S, Izzo M, Pancaldi F, Scapoli GL, Liboni A, Gemmati D. Hemochromatosis C282Y gene mutation increases the risk of venous leg ulceration. J Vasc Surg 2005;42:309-14.

PMID: 16102632

Comment: This very important study evaluated a gene for hemochromatosis and its relationship with venous ulceration. The study found that the hemochromatosis gene (HFE) C282Y mutation significantly increases the risk of ulcer in primary CVD by almost seven times. This study identifies a gene that is involved in venous ulcer and has significant implications in diagnosis, prognosis, and therapeutic interventions.

• Tognazzo S, Gemmati D, Palazzo A, Catozzi L, Carandina S, Legnaro A, Tacconi G, Scapoli GL, Zamboni P. Prognostic role of factor XIII gene variants in nonhealing venous leg ulcers. J Vasc Surg 2006;44:815-9.

PMID: 16945500

Comment: This interesting study determined that certain Factor XIII gene variants are associated with smaller venous ulcer area. The importance of Factor XIII is its function in cross-linking proteins during wound healing, and having the proper gene polymorphism promotes smaller venous ulcers.

• Gemmati D, Tognazzo S, Catozzi L, Federici F, De Palma M, Gianesini S, Scapoli GL, De Mattei M, Liboni A, Zamboni P. Influence of gene polymorphisms in ulcer healing process after superficial venous surgery. J Vasc Surg 2006;44:554-62.

PMID: 16950433

Comment: This study evaluated the importance of gene variants in determining their importance in venous ulcer healing following superficial venous surgery. The importance is that patients with the FactorXIII 34L gene variant (independent of HFE gene variant) had shorter healing times following surgery, indicating the role for Factor XIII in tissue regeneration. Furthermore, genetic analysis allows for the identification of patient with venous ulcers that may respond to modulated therapy.

• Gemmati D, Federici F, Catozzi L, Gianesini S, Tacconi G, Scapoli GL, Zamboni P. DNA-array of gene variants in venous leg ulcers: detection of prognostic indicators. J Vasc Surg 2009;50:1444-51.

PMID: 19958990

Comment: This study evaluates candidate genes that may pose increased risks for the development of venous ulcers.