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physiological processes, and existing genetic factors can aggravate the clinical situation, and vice versa.
However, unfortunately, the genetic factors that are primarily involved in pathological processes are not yet
fully understood, and we still have to understand how to formalize the genetic contribution to the
phenotype of a person with varicose veins (VVs). The role of genetics in this context can hardly be
overestimated, since genetics is one of the constituent parts, in general, of the nucleation of a protein from
DNA, where both biochemical and molecular biological processes are involved (i.e., replication,
transcription and translation, from what and how protein is synthesized). Moreover, epigenetics can play an
equally important role.

HEREDITARY CONSTITUENT OF VARICOSE VEIN PATHOGENESIS-AN OVERVIEW
The first mention of VVs in the PubMed database dates back to the early 19th century. In the first half of
the 20th century, one can find explanations of the hereditary nature of the disease, the most judicious of
[1]
which was given by the British scientist Ottley . Having presented a detailed analysis of a series of fifty cases
of VV treatment, the author concluded that inheritance occurs according to the dominant type (even taking
into account the cases of the “missed generation” - the absence of manifestation of the disease in one of the
generations), because, in general, there was a higher percentage of sufferers than with a recessive defect. In
1949, for example, as a result of histological studies, American scientists Wagner and Herbut drew
conclusions about the hereditary factor of VVD; in addition, they were inclined to believe that dilatation of
the vein wall precedes valvular insufficiency, which is usually purely functional and secondary , which was
[2]
[3,4]
subsequently supported by other scientists . The significance of genetic factors in the etiology of VVD was
also emphasized in the works of the Danish and Swedish scientists Hauge and Gundersen, who, based on
the information they collected about the parents and siblings of 250 patients, concluded that the
[5]
determination of the disease by one gene is unlikely, and inheritance seems to be multifactorial . In 1974,
Czechoslovakian scientists Matousek and Prerovsky estimated the heritability of primary varicose veins is
up to 50% upon assuming the hypothesis of polygenic inheritance . Later on, a prominent role of heredity
[6]
in the development of VVs was demonstrated by the French scientists Cornu-Thenard et al. . However,
[7]
due to the fact that their study did not include examination of siblings or the third generation, they were
unable to determine the genetic model of inheritance, and therefore they doubted autosomal dominant and
autosomal recessive inheritance models, citing possible “pros” and “cons”. A little later, in 1998, Chinese
scientists Guo and Guo, based on the results of the genetic analysis of VVD, concluded that in most cases
this disease is compatible with an autosomal dominant inheritance of incomplete penetrance, while some of
[8]
the cases were sporadic, which prompted them to assume a recessive model possible as well . Indeed, with
an autosomal dominant type of inheritance: (1) the disease is transmitted vertically and is diagnosed in each
generation, but, due to incomplete penetrance in the transmission of a trait, sometimes one generation is
skipped; (2) phenotypically “normal” family members do not transmit the disease to their offspring; and (3)
both men and women can inherit the disease with equal frequency. After analyzing the literature data , we
[9]
tend to believe that the inheritance pattern of VVD is autosomal dominant with incomplete penetrance.

Subsequently, inheritance patterns and the results of family and twin studies were examined in 2003 by the
French scientist Pistorius , who hypothesized about the possible genetic heterogeneity of VVD, suggesting
[10]
the existence of different genotypic profiles with a similar phenotype. Many studies by other scientists have
also shown a significant genetic contribution to the etiology of VVD, as reported in a review by the New
Zealand group of Krysa et al. . Since then, genetic research has continued and gained strength and
[11]
momentum. In recent decades, a lot of genetic research, particularly associative research, has been carried
out.