Heritability of Venous Function in Humans

Abstract

Objectives-Venous function contributes to the pathogenesis of thrombophlebitis, venous thrombosis, and possibly to arterial hypertension. Venous disease is presumably heritable; however, the genetic variance of venous function is unknown. Methods and Results-We determined the heritability of venous function in 46 twin pairs (24 monozygotic, age 35Ϯ11 years, 14 men, 34 women; 22 dizygotic, age 30Ϯ8 years, 19 men, 25 women). After a resting phase in the supine position, we determined venous function in both legs by impedance plethysmography. Venous capacity was determined by a standardized protocol. In addition, we obtained venous pressure volume curves by slowly deflating a thigh cuff from 60 to 0 mm Hg. Venous compliance was determined as the steepest part of the venous pressure volume curve. Heritability was estimated using a path modeling approach. Unadjusted heritability was 0.6 (PϽ0.05) for venous capacity and 0.9 (PϽ0.05) for venous compliance. The heritability estimate for venous capacity decreased to 0.3 after adjustment for age, body mass index, and body fat. The heritability estimate for venous compliance remained essentially unchanged after adjustment for sex and age. Key Words: twin study Ⅲ genetics Ⅲ plethysmography Ⅲ venous compliance A pproximately 75% of the circulating blood volume is contained in veins. Therefore, relatively small changes in venous function may have a substantial effect on the cardiovascular system. For example, an increase in venous tone may cause a shift of blood volume from the periphery toward the heart and increase cardiac output. This mechanism may contribute to increased cardiac output in the earlier stages of essential hypertension. 1,2 Venous function becomes particularly important during assumption of upright posture as 500 to 1000 mL are pooled below the diaphragm. 3 Variability in the amount of blood that is pooled during standing influences the propensity to experience orthostatic symptoms. 4 Venous function may also contribute to the pathogenesis of varicose veins, thrombophlebitis, and venous thrombosis. Thus, genes that influence venous function might play an important role in a variety of common cardiovascular ailments. Indeed, Ϸ60% of the variation in the susceptibility to venous thrombosis is related to genetic factors. 5 A positive family history substantially increases the likelihood to suffer from varicose veins, 6 vasovagal syncope, 7 or essential hypertension. However, the research on the genetics of all these conditions has largely neglected the possibility that venous function may be an important intermediate phenotype. The responsiveness of veins to adrenergic stimulation is influenced by genetic factors. 8,9 Yet, the mechanical properties of veins, such as compliance and capacity, may be more relevant to physiological function. The magnitude of the genetic contribution to these measures is not known. We determined the heritability of venous function in a cohort of normal twins. Conclusions-We Methods SubjectsWe investigated the heritability of venous ...

Mutations in FOXC2 Are Strongly Associated With Primary Valve Failure in Veins of the Lower Limb

“…A genetic predisposition to varicose veins has been proposed for many years, and venous function in twins, measured by impedance plethysmography, indicates a strong genetic influence. 6 Individuals are more likely to be affected by varicose veins when parents and siblings have varicose veins. 7 A study of 134 families reported that the risk of developing varicose veins was 90% when both parents were affected, whereas the risk was only 20% for individuals who had unaffected parents.…”

Mind the Vein

“…8 Finally, twin studies suggested that venous compliance and capacity are heritable. 9 It is tempting to speculate that genes affecting venous function could also promote hypertension. The observation of reduced venous compliance and altered arterial blood pressure responses to acute volume loading in normotensive men with positive family histories of hypertension 10 suggests that the idea is not completely off the mark.…”

HealthTwiSt: The Berlin Twin Registry for Health Research

“…Direct measurements of traits like blood pressure were extended by functional assays to determine venous function (e.g., Brinsuk et al, 2004). Molecular phenotyping has been included in one study in which we counted the percentage of neutrophils expressing Proteinase 3 on their cell surface as a potential risk factor for Wegener granulomatosis, finding a heritability of 0.99 with strong indication of epistatic effects (Schreiber et al, 2003).…”