Register
Forgot your password?

Genetic predictors of calcific valvular heart disease

Authors: Ponasenko A.V.1, Kutikhin A.G.1, Khutornaya M.V.1, Yuzhalin A.E.2, Tsepokina A.V.1, Golovkin A.S.1, Barbarash O.L.1

Company: 1 Research Institute for Complex Issues of Cardiovascular Diseases; Sosnovyy bul’var, 6, Kemerovo, 650002, Russian Federation;
2 Oxford Institute for Radiation Oncology; Roosevelt Drive, Oxford, OX3 7DQ, United Kingdom

For correspondence:  Sign in or register.

Type:  Heart valve and coronary artery calcification


DOI: https://doi.org/10.15275/kreatkard.2016.02.01

For citation: Ponasenko A.V., Kutikhin A.G., Khutornaya M.V. et al. Genetic predictors of calcific valvular heart disease. Kreativnaya Kardiologiya. 2016; 10 (2): 103-116 (in Russian)

Keywords: calcification heart valves aortic stenosis mitral annular mitral valve gene polymorphisms genetic susceptibility

Full text:  

 

Abstract

Valvular calcification precedes the development of valvular stenosis and may represent an important early phenotype for valvular heart disease. It is known that development of valvular calcification is likely to occur among members of a family. However, the knowledge about the role of genomic predictive markers in valvular calcification is still elusive. Aims of this review are to assess the impact of gene polymorphisms on risk and severity of aortic stenosis and heart valve calcification. According to the results of the investigations carried out, all polymorphisms may be divided into the three groups conferring the level of evidence of their association with these diseases. It is possible to conclude that APOB (rs1042031, and rs6725189), ACE (rs4340), IL10 (rs1800896 and rs1800872), and LPA (rs10455872) gene polymorphisms may be associated with aortic stenosis with a relatively high level of evidence. A number of other polymorphisms, such as rs1042636 polymorphism within the CaSR gene, rs3024491, rs3021094, rs1554286, and rs3024498 polymorphisms within the IL10 gene, rs662 polymorphism within the PON1 gene, rs2276288 polymorphism within the MYO7A gene, rs5194 polymorphism within the AGTR1 gene, and rs2071307 polymorphism within the ELN gene, may be associated with aortic stenosis whilst rs17659543 and rs13415097 polymorphisms within the IL1F9 gene may correlate with a risk of mitral annular calcification with a moderate level of evidence. Certain polymorphisms within the genes of calcium signaling pathway (RUNX2 and CACNA1C) are also associated with heart valve calcification with a moderate level of evidence. Finally, rs1544410 polymorphism within the VDR gene, E2 and E4 alleles within the APOE gene, rs6254 polymorphism within the PTH gene, and rs1800871 polymorphism within the IL10 gene may be associated with aortic stenosis, whereas rs4340 polymorphism within the ACE gene correlates with mitral annular calcification with a low level of evidence.

References

  1. Egorov I.V.Senile aortic stenosis: current state ofproblem (to the 110th anniversary of the I.G. Menke-berg's publication). Consilium medicum.2014; 16 (1):17–23 (in Russian).
  2. Lutay M.I., Golikova I.P.Calcification of the coro-nary arteries, aorta, heart valves and ischemic heartdisease: pathophysiology, relationship, prognosis,risk stratification. Ukrai'ns'kyj kardiologichnyj zhur-nal.2015; 2: 99–112 (in Russian).
  3. Monckerg J.G. Der normale histologische Bau und die Sklerose Aortenklappen. Virchows Arch. Pathol. Anat. Physiol. Klin. Med. 1904; 176: 472.
  4. Schoen F.J., Levy R.J. Calcification of tissue heart valve substitutes: progress toward understanding and prevention. Ann. Thorac. Surg. 2005; 79: 1072–80.
  5. An Y., Wang Y.T., Ma Y.T., Wulasihan M., Huang Y. et al. IL-10 genetic polymorphisms were associated with valvular calcification in han, uygur and kazak populations in Xinjiang, China. PLoS One. 2015; 10 (6): e0128965.
  6. Furukawa K. Recent advances in research on human aortic valve calcification. J. Pharmacol. Sci. 2014; 124: 129–37.
  7. Kutikhin A.G., Yuzhalin A.E., Brusina E.B., Ponasenko A.V., Golovkin A.S., Barbarash O.L. Genetic predisposition to calcific aortic stenosis and mitral annular calcification. Mol. Biol. Rep. 2014; 41 (9): 5645–63.
  8. Martynovich T.V., Akimova N.S., Fedotov E.A.,Shvarts Yu.G.Polymorphism of genes associatedwith increased cardiovascular risk and cognitivefunctions in patients with chronic heart failure andhealthy individuals. A pilot study. Serdechnayanedostatochnost'.2015; 2: 93–9 (in Russian).
  9. Rajamannan M., Evans F.J., Aikawa E., Grande-Allen K.J., Demer L.L. et al. Calcific aortic valve disease: not simply a degenerative process: a review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: Calcific aortic valve disease-2011 update. Circulation. 2011; 124:1783–91.
  10. Fox C.S. Vasan R.S., Parise H., Levy D., O'Donnell C.J. Mitral annular calcification predicts cardiovascular morbidity and mortality: the Framingham Heart Study. Circulation. 2003; 107: 1492–6.
  11. Li C., Xu S., Gotlieb A.I. The response to valve injury. A paradigm to understand the pathogenesis of heart valve disease. Cardiovasс. Pathol. 2011; 20: 183–90.
  12. Cosmi J.E., Kort S., Tunick P.A., Rosenzweig B.P., Freedberg R.S. et al. The risk of the development of aortic stenosis in patients with «benign» aortic valve thickening. Arch. Intern. Med. 2002; 162: 2345–7.
  13. Gaudreault N., Ducharme V., Lamontagne M., Guauque-Olarte S., Mathieu P. et al. Replication of genetic association studies in aortic stenosis in adults. Am. J. Cardiol. 2011; 108 (9): 1305–10.
  14. Vahanian A., Alfieri O., Andreotti F., Antunes M.J., Barón-Esquivias G. et al. Guidelines on the management of valvular heart disease (version 2012). Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 2012; 33: 2451–96.
  15. Bockeria L.A., Bockeria O.L., Fatulaev Z.F., Kemo-va S.Sh.Reconstruction of the fibrous ring of themitral valve in advanced calcification in conjunc-tion with surgical treatment of coronary heart dis-ease. Bulleten' Nauchnogo Tsentra Serdechno-Sosudistoy Khirurgii imeni A.N. Bakuleva RossiyskoyAkademii Meditsinskikh Nauk.2014; 15 (5): 53–8(in Russian).
  16. Probst V., Le Scouarnec S., Legendre A., Jousseaume V., Jaafar P. et al. Familial aggregation of calcific aortic valve stenosis in the western part of France. Circulation. 2006; 113 (6): 856–60.
  17. Bella J.N., Tang W., Kraja A., Rao D.C., Hunt S.C. et al. Genome-wide linkage mapping for valve calcification susceptibility loci in hypertensive sibships: the Hypertension Genetic Epidemiology Network Study. Hypertension. 2007; 49: 453–60.
  18. Duran C., Appleby N., Vardy M., Imelfort M., Edwards D., Batley J. Single nucleotide polymorphism discovery in barley using auto SNPdb. Plant. Biotechnol. J. 2009; 7 (4): 326–33.
  19. Tierney M.J., Medcalf R.L. Plasminogen activator inhibitor type 2 contains mRNA instability elements within exon 4 of the coding region. Sequence homology to coding region instability determinants in other mRNAs. J. Biol. Chem. 2001; 276: 13675–84.
  20. Mozos I., Marginean O. Links between vitamin D deficiency and cardiovascular diseases. Biomed. Res. Int. 2015; 2015: 109275.
  21. Schmidt N., Brandsch C., Kühne H., Thiele A., Hirche F., Stangl G.I. Vitamin D receptor deficiency and low vitamin D diet stimulate aortic calcification and osteogenic key factor expression in mice. PLoS One. 2012; 7 (4): e35316.
  22. Ortlepp J.R., Hoffmann R., Ohme F., Lauscher J., Bleckmann F. et al. The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis. Heart. 2001; 85: 635–8.
  23. Schmitz F., Ewering S., Zerres K., Klomfass S., Hoffmann R., Ortlepp J.R. Parathyroid hormone gene variant and calcific aortic stenosis. J. Heart Valve Dis. 2009; 18: 262–7.
  24. Alfadda T.I., Saleh A.M., Houillier P., Geibel J.P. Calcium-sensing receptor 20 years later. Am. J. Physiol. Cell. Physiol. 2014; 307 (3): C221–31.
  25. Turkmen F., Ozdemir A., Sevinc C., Eren P.A., Demiral S. Calcium-sensing receptor gene polymorphisms and cardiac valvular calcification in patients with chronic renalfailure: a pilot study. Hemodial. Int. 2009; 13: 176–80.
  26. Mathieu P., Boulanger M.C. Basic mechanisms of calcific aortic valve disease. Can. J. Cardiol. 2014; 30 (9): 982–93.
  27. Avakian S.D., Annicchino-Bizzacchi J.M., Grinberg M., Ramires J.A., Mansura A.P. Apolipoproteins AI, B, and E polymorphisms in severe aortic valve stenosis. Clin. Genet. 2001; 60: 381–4.
  28. Novaro G.M., Sachar R., Pearce G.L., Sprecher D.L., Griffin B.P. Association between apolipoprotein E alleles and calcific valvular heart disease. Circulation. 2003; 108 (15): 1804–8.
  29. Arsenault B.J., Boekholdt S.M., Dubé M.P., Rhéaume E., Wareham N.J. et al. Lipoprotein (a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort. Circ. Cardiovasc. Genet. 2014; 7 (3): 304–10.
  30. Ortlepp J.R., Pillich M., Mevissen V., Krantz C., Kimmel M., Autschbach R. et al. APOE alleles are not associated with calcific aortic stenosis. Heart. 2006; 92: 1463–6.
  31. Thanassoulis G., Campbell C.Y., Owens D.S., Smith J.G., Smith A.V. Genetic associations with valvular calcification and aortic. N. Engl. J. Med. 2013; 368 (6): 503–12.
  32. Kamstrup P.R., Tybjaerg-Hansen A., Nordestgaard B.G. Elevated lipoprotein (a) and risk of aortic valve stenosis in the general population. J. Am. Coll. Cardiol. 2014; 63 (5): 470–7.
  33. Arsenault B.J., Dubé M.P., Brodeur M.R. Evaluation of links between high-density lipoprotein genetics, functionality, and aortic valve stenosis risk in humans. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 457–62.
  34. Ortlepp J.R., Schmitz F., Mevissen V., Weiss S., Huster J. et al. The amount of calcium-deficient hexagonal hydroxyapatite in aortic valves is influenced by gender and associated with genetic polymorphisms in patients with severe calcific aortic stenosis. Eur. Heart J. 2004; 25 (6): 514–22.
  35. Goldbarg S.H., Elmariah S., Miller M.A., Fuster V. Insights into degenerative aortic valve disease. J. Am. Coll. Cardiol. 2007; 50 (13): 1205–13.
  36. Davutoglu V., Nacak M. Influence of angiotensinconverting enzyme gene insertion/deletion polymorphism on rheumatic valve involvement, valve severity and subsequent valve calcification. J. Heart Valve Dis. 2005; 14: 277–81.
  37. Ertas F.S., Hasan T., Ozdol C., Gulec S., Atmaca Y. et al. Relationship between angiotensin-converting enzyme gene polymorphism and severity of aortic valve calcification. Mayo Clin. Proc. 2007; 82: 944–50.
  38. Mattoo R.L. The roles of fibroblast growth factor (FGF)-23, α-Klotho and furin protease in calcium and phosphate homeostasis: a mini-review. Indian J. Clin. Biochem. 2014; 29 (1): 8–12.
  39. Tangri N., Alam A., Wooten E.C., Huggins G.S. Lack of association of Klotho gene variants with valvular and vascular calcification in Caucasians: a candidate gene study of the Framingham Offspring Cohort. Nephrol. Dial. Transplant. 2011; 26: 3998–4002.
  40. Moura L.M., Faria S., Brito M., Pinto F.J., Kristensen S.D. et al. Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular aortic stenosis. Am. J. Cardiovasc. Dis. 2012; 2: 123–32.
  41. Ellis S.G., Dushman-Ellis S., Luke M.M., Murugesan G., Kottke-Marchant K. et al. Pilot candidate gene analysis of patients ≥60 years old with aortic stenosis involving a tricuspid aortic valve. Am. J. Cardiol. 2012; 110: 88–92.
  42. Garg V., Muth A.N., Ransom J.F., Schluterman M.K., Barnes R. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005; 437: 270–4.
  43. Garg V. Molecular genetics of aortic valve disease. Curr. Opin. Cardiology. 2006; 213: 180–4.
  44. Bosse K., Hans C.P., Zhao N., Koenig S.N., Huang N. et al. Endothelial nitric oxide signaling regulates Notch1 in aortic valve disease. J. Mol. Cell. Cardiol. 2013; 60: 27–35.
  45. Ducharme V., Guauque-Olarte S., Gaudreault N., Pibarot P., Mathieu P., Bossé Y. NOTCH1 genetic variants in patients with tricuspid calcific aortic valve stenosis. J. Heart Valve Dis. 2013; 22 (2): 142–9.
  46. Guauque-Olarte S., Messika-Zeitoun D., Droit A., Lamontagne M., Tremblay-Marchand J. et al. Calcium signaling pathway genes RUNX2 and CACNA1C are associated with calcific aortic valve disease. Circ. Cardiovasc. Genet. 2015; 8 (6): 812–22.
  47. Egorov I.V., Shostak N.A., Artyukhina E.A.Aorticstenosis is a degenerative genesis – the problem atthe intersection of opinions. Rossiyskiy kardio-logicheskiy zhurnal.1999; 4: 50–3 (in Russian).
  48. Tsurko V.V.Osteoporosis, tissue calcification andatherogenesis: the trigger role of calcium and vita-min D. Klinicheskaya gerontologiya.2009; 15 (2):3–8 (in Russian).
  49. Chipigina N.S., Urvacheva G.M., Shostak N.A. Clini-cal importance of idiopathic mitral annular calcifi-cation. Racional'naya farmakoterapiya v kardiologii.2011; 7 (4): 483–6 (in Russian).
  50. Nordström P., Glader C.A., Dahlén G., Birgander L.S., Lorentzon R. et al. Oestrogen receptor alpha gene polymorphism is related to aortic valve sclerosis in postmenopausal women. J. Intern. Med. 2003; 254: 140–6.

About Authors

  • Ponasenko Anastasiya Valerievna, MD, PhD, Chief of Laboratory;
  • Kutikhin Anton Gennad'evich, Junior Research Associate;
  • Khutornaya Mariya Vladimirovna, Junior Research Associate;
  • Yuzhalin Arseniy Evgen'evich, Postgraduate;
  • Tsepokina Anna Viktorovna, Junior Research Associate;
  • Golovkin Aleksey Sergeevich, MD, DM, Senior Research Associate;
  • Barbarash Ol'ga Leonidovna, MD, DM, Professor, Director of Research Institute for Complex Issues of Cardiovascular Diseases

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Sort by