title: 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.
authors.affiliation: Center for Cardiovascular and Pulmonary Research and The Heart Center, Room WB4221, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: LaHaye
authors.forename: Joy
authors.initials: J
authors.lastname: Lincoln
authors.forename: Vidu
authors.initials: V
authors.lastname: Garg
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use; D001021:Aortic Valve / Q000002:abnormalities; D000082882:Bicuspid Aortic Valve Disease; D002648:Child; D004437:Ebstein Anomaly / Q000453:epidemiology / Q000235:genetics; D055106:Genome-Wide Association Study; D006330:Heart Defects, Congenital / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D006349:Heart Valve Diseases / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D006353:Heart-Assist Devices / Q000706:statistics & numerical data / Q000639:trends; D006801:Humans; D008017:Life Expectancy; D008945:Mitral Valve Prolapse / Q000453:epidemiology / Q000235:genetics; D015995:Prevalence; D011666:Pulmonary Valve Stenosis / Q000453:epidemiology / Q000235:genetics
chemical_list: D000925:Anticoagulants
references.citation: Hum Mol Genet. 2006 Aug 15;15(16):2457-67
references.pmid: 16825286
references.citation: BMC Med Genet. 2013 Apr 11;14:44
references.pmid: 23578328
references.citation: Cardiovasc Res. 2012 Oct 1;96(1):109-19
references.pmid: 22843703
references.citation: Circ Cardiovasc Genet. 2011 Feb;4(1):43-50
references.pmid: 21127202
references.citation: Orphanet J Rare Dis. 2013 Apr 12;8:58
references.pmid: 23587214
references.citation: Pediatrics. 2007 Jun;119(6):e1325-31
references.pmid: 17515436
references.citation: Circulation. 2004 Nov 9;110(19):3143-8
references.pmid: 15520309
references.citation: Arch Intern Med. 1986 Jan;146(1):119-21
references.pmid: 3942444
references.citation: Dev Cell. 2012 Feb 14;22(2):244-54
references.pmid: 22340493
references.citation: Cardiovasc Pathol. 2009 Sep-Oct;18(5):253-61
references.pmid: 18835790
references.citation: Tex Heart Inst J. 2010;37(1):99-101
references.pmid: 20200638
references.citation: Circulation. 2002 Aug 20;106(8):900-4
references.pmid: 12186790
references.citation: Development. 1997 Jun;124(11):2099-117
references.pmid: 9187138
references.citation: J Am Coll Cardiol. 2010 Jun 22;55(25):2789-800
references.pmid: 20579534
references.citation: Hum Mutat. 2008 Aug;29(8):992-1006
references.pmid: 18470943
references.citation: Circ Res. 2011 Jul 8;109(2):183-92
references.pmid: 21597012
references.citation: Nature. 1991 Jul 25;352(6333):334-7
references.pmid: 1852207
references.citation: J Clin Invest. 2011 Jul;121(7):2876-87
references.pmid: 21633169
references.citation: J Thorac Cardiovasc Surg. 2007 Aug;134(2):290-6
references.pmid: 17662764
references.citation: Matrix Biol. 2010 May;29(4):304-16
references.pmid: 20096780
references.citation: J Biol Chem. 2001 May 25;276(21):17871-7
references.pmid: 11278410
references.citation: Circ Res. 2009 Aug 28;105(5):408-21
references.pmid: 19713546
references.citation: J Med Genet. 2004 Jul;41(7):e97
references.pmid: 15235040
references.citation: Genet Med. 2010 Oct;12(10):597-605
references.pmid: 20847697
references.citation: Biochem Biophys Res Commun. 2006 Jul 14;345(4):1460-5
references.pmid: 16729972
references.citation: N Engl J Med. 2013 Feb 7;368(6):503-12
references.pmid: 23388002
references.citation: Circulation. 2007 Jan 2;115(1):40-9
references.pmid: 17190868
references.citation: Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):161-79
references.pmid: 21396583
references.citation: Dev Biol. 2004 May 15;269(2):505-18
references.pmid: 15110716
references.citation: Dev Dyn. 2006 Dec;235(12):3295-305
references.pmid: 17029294
references.citation: PLoS One. 2012;7(4):e35539
references.pmid: 22536403
references.citation: Genes Dev. 2004 Jan 1;18(1):99-115
references.pmid: 14701881
references.citation: Science. 1999 Mar 26;283(5410):2080-2
references.pmid: 10092230
references.citation: Nature. 2003 Jul 24;424(6947):443-7
references.pmid: 12845333
references.citation: Nature. 2005 Sep 8;437(7056):270-4
references.pmid: 16025100
references.citation: Heart Lung Circ. 2008 Oct;17(5):357-63
references.pmid: 18514024
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4736-41
references.pmid: 19251646
references.citation: J Mol Cell Cardiol. 2013 Dec;65:137-46
references.pmid: 24157418
references.citation: Anat Rec. 2000 Feb 1;258(2):119-27
references.pmid: 10645959
references.citation: J Anat. 2012 Jan;220(1):92-101
references.pmid: 22034929
references.citation: J Mol Cell Cardiol. 2012 Aug;53(2):277-81
references.pmid: 22641149
references.citation: Circulation. 2005 Feb 22;111(7):832-4
references.pmid: 15723989
references.citation: Annu Rev Genomics Hum Genet. 2005;6:45-68
references.pmid: 16124853
references.citation: Int J Cardiol. 1992 Mar;34(3):249-54
references.pmid: 1563849
references.citation: Circulation. 2013 Jan 1;127(1):e6-e245
references.pmid: 23239837
references.citation: Nat Genet. 2003 Mar;33(3):407-11
references.pmid: 12598898
references.citation: J Mol Cell Cardiol. 2009 Dec;47(6):828-34
references.pmid: 19695258
references.citation: Circ Res. 2013 May 24;112(11):1420-32
references.pmid: 23584254
references.citation: J Clin Invest. 2004 Dec;114(11):1586-92
references.pmid: 15546004
references.citation: Mayo Clin Proc. 2010 May;85(5):483-500
references.pmid: 20435842
references.citation: Cell Mol Life Sci. 2006 May;63(10):1141-8
references.pmid: 16568242
references.citation: Am J Med Genet A. 2013 Dec;161A(12):3187-90
references.pmid: 23956225
references.citation: J Card Surg. 2013 Mar;28(2):139-43
references.pmid: 23347109
references.citation: Am J Cardiol. 1986 Oct 1;58(9):762-7
references.pmid: 3766417
references.citation: Dev Biol. 2006 Jun 15;294(2):292-302
references.pmid: 16643886
references.citation: Circulation. 2001 Nov 20;104(21):2525-32
references.pmid: 11714645
references.citation: Curr Opin Cardiol. 2007 May;22(3):171-5
references.pmid: 17413272
references.citation: Annu Rev Physiol. 2011;73:29-46
references.pmid: 20809794
references.citation: Dev Biol. 2012 Jun 15;366(2):111-24
references.pmid: 22546693
references.citation: Heart. 2011 Aug;97(15):1193-5
references.pmid: 21459929
references.citation: Nat Genet. 2000 Feb;24(2):171-4
references.pmid: 10655064
references.citation: J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900
references.pmid: 12084585
references.citation: Nat Genet. 2005 Mar;37(3):275-81
references.pmid: 15731757
references.citation: J Am Coll Cardiol. 2004 Jul 7;44(1):138-43
references.pmid: 15234422
references.citation: Am J Hum Genet. 1999 Nov;65(5):1242-51
references.pmid: 10521289
references.citation: Circ Res. 1998 Jun 1;82(10):1043-52
references.pmid: 9622157
references.citation: Heart. 2000 Jan;83(1):81-5
references.pmid: 10618341
references.citation: Circulation. 2000 May 23;101(20):2345-8
references.pmid: 10821808
references.citation: BMC Dev Biol. 2011 Oct 19;11:62
references.pmid: 22011202
references.citation: Hypertension. 2007 Mar;49(3):453-60
references.pmid: 17224468
references.citation: Cardiovasc Pathol. 2011 May-Jun;20(3):162-7
references.pmid: 20705485
references.citation: Dev Biol. 2007 May 1;305(1):120-32
references.pmid: 17350610
references.citation: Nature. 1991 Jul 25;352(6333):337-9
references.pmid: 1852208
references.citation: J Mol Cell Cardiol. 2013 Jul;60:27-35
references.pmid: 23583836
references.citation: Physiology (Bethesda). 2005 Dec;20:390-7
references.pmid: 16287988
references.citation: Gene. 2014 Jan 25;534(2):320-3
references.pmid: 24498650
references.citation: J Mol Cell Cardiol. 2013 Jul;60:50-9
references.pmid: 23531444
references.citation: Nature. 1991 Jul 25;352(6333):330-4
references.pmid: 1852206
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19836-41
references.pmid: 17172441
references.citation: Nat Rev Genet. 2008 Jan;9(1):49-61
references.pmid: 18071321
references.citation: Am Heart J. 1986 Dec;112(6):1359-62
references.pmid: 3538838
references.citation: Am J Med Genet. 1986 Jul;24(3):387-92
references.pmid: 3728560
references.citation: Br Heart J. 1989 Mar;61(3):292-9
references.pmid: 2930668
references.citation: N Engl J Med. 1999 Jul 1;341(1):1-7
references.pmid: 10387935
references.citation: J Cardiovasc Transl Res. 2011 Dec;4(6):748-56
references.pmid: 21773876
references.citation: PLoS Genet. 2012;8(5):e1002690
references.pmid: 22589735
references.citation: PLoS One. 2011;6(11):e27743
references.pmid: 22110751
references.citation: Circulation. 2006 Feb 14;113(6):856-60
references.pmid: 16461814
references.citation: Br Heart J. 1989 Mar;61(3):300-6
references.pmid: 2930669
references.citation: Science. 2006 Apr 7;312(5770):117-21
references.pmid: 16601194
references.citation: Hum Mutat. 2012 Apr;33(4):720-7
references.pmid: 22275001
references.citation: Circ Res. 2006 Jun 9;98(11):1431-8
references.pmid: 16645142
references.citation: Nat Med. 2004 Aug;10(8):849-57
references.pmid: 15273746
references.citation: Curr Opin Genet Dev. 2007 Feb;17(1):15-22
references.pmid: 17208427
references.citation: Cell. 2004 Sep 3;118(5):649-63
references.pmid: 15339668
references.citation: Cardiovasc Pathol. 2009 Jul-Aug;18(4):191-7
references.pmid: 18621549