Genetics of Valvular Heart Disease

Abstract

Valvular heart disease is associated with significant morbidity and mortality and often the result of congenital malformations. However, the prevalence is increasing in adults not only because of the growing aging population, but also because of improvements in the medical and surgical care of children with congenital heart valve defects. The success of the Human Genome Project and major advances in genetic technologies, in combination with our increased understanding of heart valve development, has led to the discovery of numerous genetic contributors to heart valve disease. These have been uncovered using a variety of approaches including the examination of familial valve disease and genome-wide association studies to investigate sporadic cases. This review will discuss these findings and their implications in the treatment of valvular heart disease.

Genetic basis of aortic valvular disease

“…BAV is the most prevalent birth defect, and population based studies have supported a strong genetic component along with other left-sided cardiac malformations [10]. Initial insight into the genetic etiology of BAV came from studies of familial BAV where mutations in NOTCH1 were discovered to segregate in families with autosomal-dominant valve disease [11].…”

Mitral Valve Prolapse: Current Views and Challenges (Review)

“…Defects of other variants of filamin genes (B and C) were not accompanied by cardiovascular defects in the experiment on mutant mice [124,125]. Pathology of the valves may be realized through the impaired signaling function of filamin A, which coordinates localization and activity of TGF-β receptors-activators of SMAD, especially SMAD2, and can serve as a positive regulator of TGF-β signaling [90,126, 127]. Mutations in the filamin A may explain the similarity of clinical manifestations of Marfan syndrome and non-syndromic MVP, since both these states are characterized by TGF-β activity increase.…”

“…Marfan syndrome is associated with mutations in the FBN1 gene located on 15q15-q21 chromosome [85,90,101, 102], it may also be caused by mutation in gene TGF-β located on the 3p24.2-р25 chromosome [21,103]. The role of FBN1 and TGF-β mutation in MVP pathogenesis was confirmed by the experiment on mice with the model of Marfan syndrome [104].…”

“…TGF-β is a protein controlling a number of physiological processes including angiogenesis, proliferation, cellular differentiation and reviews apoptosis of the majority of cells [85,89,90]. This representative of cytokines exerts multidirectional action on the extracellular matrix structure.…”

“…Klemenov СТМ ∫ 2017 -vol. 9, No.3 129 reviews apoptosis of the majority of cells [85, 89,90]. This representative of cytokines exerts multidirectional action on the extracellular matrix structure.…”