A Genetic Study of Chronic Venous Insufficiency

doi:10.1016/j.avsg.2011.11.036

Annals of Vascular Surgery

Volume 26, Issue 5, July 2012, Pages 636-642

https://doi.org/10.1016/j.avsg.2011.11.036 Get rights and content

Background

Chronic venous insufficiency (CVI) is an important cause of morbidity in Western countries. The aim of this study is to demonstrate the heredity of CVI, focusing on molecular and genetic aspects of the disease.

Methods

The study depended on the recruitment of informative families, accurate determination of the phenotype of each family member, and blood sample for DNA extraction for genetic analysis. Each family member was invited to attend a vascular consultation. A genealogical tree for each recruited family was composed. Then, a peripheral blood sample for DNA extraction from each member of the recruited families was obtained for genetic evaluation.

Results

By the evaluation of genealogical trees, it was evident that CVI segregates, in all families studied, in an autosomal dominant mode with incomplete penetrance. In nine families studied, varicose veins were linked to the candidate marker D16S520 on chromosome 16q24, which may account for the linkage to FOXC2.

Conclusion

In our study, in families with affected patients with the D16S520 marker, there was evidence of saphenofemoral junction reflux. The fact that there is linkage to a candidate marker for the FOXC2 gene suggests there is a functional variant within, or in the vicinity of, which predisposes to varicose veins. Further studies are necessary to identify genes and mechanism so as to achieve better understanding of the genetic basis of CVI.

Introduction

Chronic venous insufficiency (CVI) is an important cause of morbidity in Western countries. The clinical manifestations of CVI range from varicose veins and mild swelling to more severe changes, such as edema, pigmentation, induration, and ulceration.¹

The prevalence of CVI varies widely, from 56% in men to 60% in women,1, 2 and CVI represents an important socioeconomic impact in Western countries because of the major distribution of the disease and its complications in working people. Risk factors for varicose veins include female sex, standing occupations, overweight, number of pregnancies, and older age.

It is evident, nevertheless, that risk factors themselves do not cause the disease. In previous studies, physicians have found that 70% to 80% of their patients with varicose veins have a family history of the disease.3, 4

A study focused on linkage with the candidate marker D16S520 on chromosome 16, which is located near the gene FOXC2.⁵

The aim of this study is to demonstrate the heredity of CVI, focusing on molecular and genetic aspects of the disease.

Section snippets

Methods

The study depended on the recruitment of informative families, accurate determination of the phenotype of each family member, and blood samples for DNA extraction for genetic analysis. Each family member was invited to attend a vascular consultation where they were clinically examined and underwent duplex ultrasound evaluation.

Institutional review board approval was obtained.

The studied families included patients suffering from CVI and enrolled at our department from whom it was possible to

Results

From the observation of the genealogical trees of this study, it is evident that CVI segregates, in all studied families, in an autosomal dominant mode with incomplete penetrance.

In nine families (2, 3, 6, 7, 10, 11, 13, 17, and 18) of this study, varicose veins were linked to the candidate marker D16S520 on chromosome 16q24 (Table II).

In these 9 families, all 44 affected individuals (6 male, 38 female) (44% of total affected individuals) showed isolated reflux of the great saphenous/femoral

Discussion

Etiologic factors responsible for structural changes observed in varicose veins are poorly understood.

The factors involved and described later are venous hypertension, venous wall alteration, endothelium and extracellular matrix (ECM), and genetic influence.

Venous hypertension due to valvular insufficiency may not be primarily responsible for the structural changes observed in these veins,6, 7, 8 as previously believed. However, a possible molecular mechanism linking the hemodynamic changes of

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Clinical ResearchA Genetic Study of Chronic Venous Insufficiency

Background

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

J Vasc Surg

Eur J Vasc Endovasc Surg

J Surg Res

Dev Biol

J Biol Chem

Epidemiology of chronic venous disease

Phlebology

Heredity of varicose veins

J Rev Med

Heredity of varices

Phlebologie

Lymphoedema Consortium. Linkage to the FOXC2 region of chromosome 16 for varicose veins in otherwise healthy, unselected sibling pairs

J Med Genet

Some thoughts on aetiology of varicose veins

J Cardiovasc Surg

Clinical Research
A Genetic Study of Chronic Venous Insufficiency