Primary varicose veins (PVV; OMIM 192200) are one of the most common vascular abnormalities, especially in northern and western Europe, affecting up to 40% of men and up to 51% of women. According to the CEAP guidelines for chronic venous disease (CVD), PVV patients with dilated subcutaneous veins of at least 3 mm diameter and without signs of edema or skin changes, are classified as C2. Patients with chronic vein insufficiency (CVI) can be classified as either C3 (edema), C4 (skin changes without ulceration), C5 (healed venous ulcer) or C6 (active venous ulcer). By this definition, CVD represents a summary term comprising patients with either PVV or CVI. The prevalence of CVI is considerably lower than that of PVV, with estimations ranging from 7 to 15% in men and from 5 to 18% in women, respectively.
Despite the frequency of CVD, the underlying etiology and pathophysiology are still poorly understood. Hormonal changes, age, female gender, pregnancy, obesity and standing occupations are environmental risk factors that predispose individuals to the dilatation, elongation and tortuosity of the saphenous vein and its tributaries. In addition, a genetic component has been proposed for many years, strongly indicated by reports on familial clustering and twin studies. The narrow-sense heritability of PVV and CVD has recently been estimated to equal 18.5% and 17.3%, respectively, in a large sample of affected nuclear families from Germany. These high heritability estimates suggest the existence of susceptibility genes, necessitating large systematic association studies.