title: [Gene polymorphisms leading to calcified and stenotic aortic valves].
abstract: In the Caucasian world calcified and stenosed aortic valves are a common disease. Due to increasing life expectancy prevalence of aortic valve disease will increase dramatically. In order to establish alternative therapeutic approaches to valve replacement, we have to get a better understanding of the pathophysiological process and genetic determinations leading to calcified and stenotic valve disease. Exploring these genetic determinations will open new specific fields of therapeutic modulations of the disease process. In the literature, different gene polymorphisms have been characterized to develop calcifications and further stenosis of the aortic valves.Here, congestive polyvalent aortic valve abnormalities without specific genetic determinations (i. e., DiGeorge syndrome or fragile x syndrome), autosomal inherited alterations leading to congestive aortic valve disease (i. e., Williams-Beuren syndrome, Gaucher's disease, tetralogy of Fallot, genetic aberrations of chromosomes 2 and 4 as well as trisomy 18), X- and Y-chromosomal specific alterations (i. e., Turner syndrome), congestive structure-based aortic valve disease (i. e., bicuspid aortic valve with regard to hand-heart syndromes, tetracuspid aortic valve associated with DiGeorge syndrome) and genetic mutations of specific target genes (i. e., epidermal growth factor receptor, NOTCH-1, elastin, angiotensin I conversion enzyme, beta-glucocerebrosidase, interleukin-10, chemokine receptor 5, connective tissue growth factor, transforming growth factor beta1, vitamin D receptor, estrogen receptor-alpha, apolipoproteins A1, B, and E) are summarized. The roles of gene polymorphism in the development of calcified and stenosed aortic valve appear slowly in the understanding of the process leading to the valve disease and are mainly based on studies of supravalvular and bicuspid aortic valve stenoses. New molecular biological methods enabling broad gene expression analyses demonstrate the similarity in the pathophysiology of atherosclerotic vessel inflammation, bone formation/fibrosis, with the processes leading to stenosed and calcified aortic valves. Based on to-date knowledge, further analyses have to be done and will improve understanding of the pathophysiological processes with regard to the development of new therapeutic drug targets.
authors.affiliation: Medizinische Klinik II, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen-Nürnberg. thomas.anger@med2.imed.uni-erlangen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Anger
authors.forename: Arif B
authors.initials: AB
authors.lastname: Ekici
authors.forename: Werner G
authors.initials: WG
authors.lastname: Daniel
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Garlichs
mesh_terms: D001021:Aortic Valve / Q000002:abnormalities; D001024:Aortic Valve Stenosis / Q000145:classification / Q000209:etiology / Q000235:genetics*; D002114:Calcinosis / Q000235:genetics*; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D005776:Gaucher Disease / Q000150:complications / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D012730:Sex Chromosomes / Q000235:genetics; D013771:Tetralogy of Fallot / Q000150:complications / Q000235:genetics; D014178:Translocation, Genetic; D014424:Turner Syndrome / Q000150:complications / Q000235:genetics; D018980:Williams Syndrome / Q000150:complications / Q000235:genetics