Chronic venous insufficiency: the genetic influence

Abstract

Many contributing factors are involved in the genesis of varicose disease of the lower limbs such as age, sex, heredity, sedentary life style among others. For physicians the decisive role played by heredity leaves no doubt. Few studies have, however, attempted to prove the importance of the hereditary factor on a clinical level, and no study has been conducted in molecular genetics. The impact of the hereditary factor is variably estimated and its nature is open to discussion. Despite the numerous limits of the research focusing on the hereditary aspect of varicose disease, the authors can nevertheless claim that the genetic factor definitively exists and has a great impact. There are few studies conducted among twins. The data collected in these studies point to the reality of various types of heredity. With the predominant impact of the hereditary factor, and despite the role played by environmental factors, it can be supposed that a single genetic anomaly may be the determining factor of the disease in a given family. Thus we have conducted an original study in order to identify one or several mutations predisposing to varicose disease, based on the approach called "reverse genetic" and linkage study. The study of a first family whose varicose disease segregates in an autosomal dominant manner allowed us to identify 3 potential loci, if we accept the hypothesis of 2 or 3 phenocopies. No candidate gene has been singled out in these regions in the first analysis. The study of a second family whose phenotype of the varicose disease is particularly homogeneous and segregates in an autosomal dominant manner did not confirm any of the previously identified loci, probably related to a genetic heterogeneity of the varicose disease. As a consequence, the second part of this study was devoted to determining the complete genotype of each individual within this family, in order to identify new loci of interest. A potential locus has just been identified. The third part of this research, currently being pursued, is devoted to the sequencing of potential genes. In parallel, the analysis of new large families is underway. The presentation will include an update on the hereditary and genetic aspects of varicose disease, and secondly identify the limits and difficulties of the genetic study of the families.