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Genetics and heritability of coronary artery disease and myocardial infarction

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A positive family history is frequently reported by patients with coronary artery disease (CAD) or myocardial infarction. For risk stratification, it is crucial to distinguish between accidental reoccurrence of sporadic cases and cases with a true heritable component of the conditions. A familial predisposition is assumed when a myocardial infarction is diagnosed by a male first degree relative before the 55th year of life or a female first degree relative before the 65th year of life. The current manuscript reviews major studies from which a familial risk of CAD or myocardial infarction can be inferred. Moreover, a brief overview summarizes the current results of molecular genetic research on chromosomal loci and genes relevant for CAD and myocardial infarction.

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References

  1. Tunstall-Pedoe H, Vanuzzo D, Hobbs M, Mahonen M, Cepaitis Z, Kuulasmaa K, Keil U (2000) Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations. Lancet 355:688–700

    Article  PubMed  CAS  Google Scholar 

  2. Tolonen H, Keil U, Ferrario M, Evans A (2005) Prevalence, awareness and treatment of hypercholesterolaemia in 32 populations: results from the WHO MONICA Project. Int J Epidemiol 34:181–192

    Article  PubMed  Google Scholar 

  3. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364:937–952

    Article  PubMed  Google Scholar 

  4. McQueen MB, Bertram L, Rimm EB, Blacker D, Santangelo SL (2003) A QTL genome scan of the metabolic syndrome and its component traits. BMC Genet 4(Suppl 1):S96

    Article  PubMed  Google Scholar 

  5. Tolg R, Witt M, Schwarz B, Kurz T, Kurowski V, Hartmann F, Geist V, Richardt G (2006) Comparison of carvedilol and metoprolol in patients with acute myocardial infarction undergoing primary coronary intervention – the PASSAT Study. Clin Res Cardiol 95:31–41

    Article  PubMed  CAS  Google Scholar 

  6. Basat O, Ucak S, Seber S, Oztekin E, Altuntas Y (2006) After myocardial infarction carvedilol improves insulin resistance compared to metoprolol. Clin Res Cardiol 95:99–104

    Article  PubMed  Google Scholar 

  7. Scheuner MT (2004) Clinical application of genetic risk assessment strategies for coronary artery disease: genotypes, phenotypes, and family history. Prim Care 31:711-xii

    PubMed  Google Scholar 

  8. Broeckel U, Hengstenberg C, Mayer B, Holmer S, Martin LJ, Comuzzie AG, Blangero J, Nurnberg P, Reis A, Riegger GA, Jacob HJ, Schunkert H (2002) A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet 30:210–214

    Article  PubMed  CAS  Google Scholar 

  9. Frantz S, Brandes RP, Hu K, Rammelt K, Wolf J, Scheuermann H, Ertl G, Bauersachs J (2006) Left ventricular remodeling after myocardial infarction in mice with targeted deletion of the NADPH oxidase subunit gp91PHOX. Basic Res Cardiol 101:127–132

    Article  PubMed  CAS  Google Scholar 

  10. Koch KC, Schaefer WM, Liehn EA, Rammos C, Mueller D, Schroeder J, Dimassi T, Stopinski T, Weber C (2006) Effect of catheter-based transendocardial delivery of stromal cellderived factor 1alpha on left ventricular function and perfusion in a porcine model of myocardial infarction. Basic Res Cardiol 101:69–77

    Article  PubMed  CAS  Google Scholar 

  11. Gallagher G, Menzie S, Huang Y, Jackson C, Hunyor SN (2006) Regional cardiac dysfunction is associated with specific alterations in inflammatory cytokines and matrix metalloproteinases after acute myocardial infarction in sheep. Basic Res Cardiol

  12. Schachinger V, Britten MB, Zeiher AM (2006) Diabetes mellitus and coronary artery disease-a high risk combination. Clin Res Cardiol 95 (Suppl 1):i18–i26

    Article  PubMed  Google Scholar 

  13. Motz W, Kaiser R (2006) Stent therapy with diabetic patients who have coronary artery disease. Clin Res Cardiol 95:i27–i30

    Article  PubMed  Google Scholar 

  14. Bischoff B, Silber S, Richartz BM, Pieper L, Klotsche J, Wittchen HU (2006) Inadequate medical treatment of patients with coronary artery disease by primary care physicians in Germany. Clin Res Cardiol 95:405–412

    Article  PubMed  CAS  Google Scholar 

  15. Hawe E, Talmud PJ, Miller GJ, Humphries SE (2003) Family history is a coronary heart disease risk factor in the Second Northwick Park Heart Study. Ann Hum Genet 67:97–106

    Article  PubMed  CAS  Google Scholar 

  16. Myers RH, Kiely DK, Cupples LA, KANNEL WB (1990) Parental history is an independent risk factor for coronary artery disease: the Framingham Study. Am Heart J 120:963–969

    Article  PubMed  CAS  Google Scholar 

  17. Murabito JM, Pencina MJ, Nam BH, D’Agostino RB Sr, Wang TJ, Lloyd- Jones D, Wilson PW, O’Donnell CJ (2005) Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults. JAMA 294:3117–3123

    Article  PubMed  CAS  Google Scholar 

  18. Boer JM, Feskens EJ, Verschuren WM, Seidell JC, Kromhout D (1999) The joint impact of family history of myocardial infarction and other risk factors on 12-year coronary heart disease mortality. Epidemiology 10:767–770

    Article  PubMed  CAS  Google Scholar 

  19. Horne BD, Camp NJ, Muhlestein JB, Cannon-Albright LA (2006) Identification of excess clustering of coronary heart diseases among extended pedigrees in a genealogical population database. American Heart Journal (in press)

  20. Hengstenberg C, Holmer SR, Mayer B, Engel S, Schneider A, Lowel H, Riegger GA, Schunkert H (2001) Siblings of myocardial infarction patients are overlooked in primary prevention of cardiovascular disease. Eur Heart J 22:926–933

    Article  PubMed  CAS  Google Scholar 

  21. Andresdottir MB, Sigurdsson G, Sigvaldason H, Gudnason V (2002) Fifteen percent of myocardial infarctions and coronary revascularizations explained by family history unrelated to conventional risk factors. The Reykjavik Cohort Study. Eur Heart J 23:1655–1663

    PubMed  CAS  Google Scholar 

  22. Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U (1994) Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med 330:1041–1046

    Article  PubMed  CAS  Google Scholar 

  23. Fischer M, Broeckel U, Holmer S, Baessler A, Hengstenberg C, Mayer B, Erdmann J, Klein G, Riegger G, Jacob HJ, Schunkert H (2005) Distinct heritable patterns of angiographic coronary artery disease in families with myocardial infarction. Circulation 111:855–862

    Article  PubMed  Google Scholar 

  24. Fischer M, Mayer B, Baessler A, Riegger G, Hengstenberg C, Schunkert H (2006) Hauptstammstenose bei Geschwistern als Prädiktor für fatale und nicht-fatale Herzinfarkte. Abstract, DGK Jahrestagung 2006, Mannheim

  25. Schunkert H, Fischer M (2002) Old and simple tools may do better – sometimes. Eur Heart J 23:1900–1902

    Article  PubMed  CAS  Google Scholar 

  26. Werneck-de-Castro JP, Costa-E-Sousa RH, de Oliveira PF, Pinho-Ribeiro V, Mello DB, Pecanha R, Mattos E, Olivares EL, Maia AC, Mill JG, Goldenberg RC, Campos-de-Carvalho AC (2006) G-CSF does not improve systolic function in a rat model of acute myocardial infarction. Basic Res Cardiol (in press)

  27. Beer S, Reincke M, Kral M, Lie SZ, Steinhauer S, Schmidt HH, Allolio B, Neubauer S (2002) Susceptibility to cardiac ischemia/reperfusion injury is modulated by chronic estrogen status. J Cardiovasc Pharmacol 40:420–428

    Article  PubMed  CAS  Google Scholar 

  28. Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359:641–644

    Article  PubMed  CAS  Google Scholar 

  29. Schunkert H, Hense HW, Holmer SR, Stender M, Perz S, Keil U, Lorell BH, Riegger GA (1994) Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med 330:1634–1638

    Article  PubMed  CAS  Google Scholar 

  30. Holmer SR, Bickeboller H, Hengstenberg C, Rohlmann F, Engel S, Lowel H, Mayer B, Erdmann J, Baier C, Klein G, Riegger GA, Schunkert H (2003) Angiotensin converting enzyme gene polymorphism and myocardial infarction a large association and linkage study. Int J Biochem Cell Biol 35:955–962

    Article  PubMed  CAS  Google Scholar 

  31. Kuznetsova T, Staessen JA, Wang JG, Gasowski J, Nikitin Y, Ryabikov A, Fagard R (2000) Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis. J Hum Hypertens 14:447–454

    Article  PubMed  CAS  Google Scholar 

  32. Schunkert H (1998) Controversial association of left ventricular hypertrophy and the ACE I/D polymorphism – is the mist clearing up? Nephrol Dial Transplant 13:1109–1112

    Article  PubMed  CAS  Google Scholar 

  33. Kolovou G, Daskalova D, Mikhailidis DP (2003) Apolipoprotein E polymorphism and atherosclerosis. Angiology 54:59–71

    PubMed  Google Scholar 

  34. Hansson GK (2001) Immune mechanisms in atherosclerosis. Arterioscler Thromb Vasc Biol 21:1876–1890

    PubMed  CAS  Google Scholar 

  35. Chiappelli M, Tampieri C, Tumini E, Porcellini E, Caldarera CM, Nanni S, Branzi A, Lio D, Caruso M, Hoffmann E, Caruso C, Licastro F (2005) Interleukin-6 gene polymorphism is an age-dependent risk factor for myocardial infarction in men. International Journal of Immunogenetics 32:349–353

    Article  PubMed  CAS  Google Scholar 

  36. Bennet AM, van Maarle MC, Hallqvist J, Morgenstern R, Frostegard J, Wiman B, Prince JA, de Faire U (2006) Association of TNF-[alpha] serum levels and TNFA promoter polymorphisms with risk of myocardial infarction. Atherosclerosis (in press)

  37. Holloway JW, Yang IA, Ye S (2005) Variation in the toll-like receptor 4 gene and susceptibility to myocardial infarction. Pharmacogenet Genomics 15:15–21

    Article  PubMed  CAS  Google Scholar 

  38. Lane DA, Grant PJ (2000) Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood 95:1517–1532

    PubMed  CAS  Google Scholar 

  39. Wang X, Ishimori N, Korstanje R, Rollins J, Paigen B (2005) Identifying novel genes for atherosclerosis through mouse-human comparative genetics. Am J Hum Genet 77:1–15

    Article  PubMed  CAS  Google Scholar 

  40. Wang L, Fan C, Topol SE, Topol EJ, Wang Q (2003) Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Science 302:1578–1581

    Article  PubMed  CAS  Google Scholar 

  41. Hayashi M, Kim SW, Imanaka-Yoshida K, Yoshida T, Abel ED, Eliceiri B, Yang Y, Ulevitch RJ, Lee JD (2004) Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure. J Clin Invest 113:1138–1148

    Article  PubMed  CAS  Google Scholar 

  42. Bhagavatula MR, Fan C, Shen GQ, Cassano J, Plow EF, Topol EJ, Wang Q (2004) Transcription factor MEF2A mutations in patients with coronary artery disease. Hum Mol Genet 13:3181–3188

    Article  PubMed  CAS  Google Scholar 

  43. Gonzalez P, Garcia-Castro M, Reguero JR, Batalla A, Ordonez AG, Palop RL, Lozano I, Montes M, Alvarez V, Coto E (2005) The Pro279Leu variant in the transcription factor MEF2A is associated with myocardial infarction. J Med Genet

  44. Weng L, Kavaslar N, Ustaszewska A, Doelle H, Schackwitz W, Hebert S, Cohen JC, McPherson R, Pennacchio LA (2005) Lack of MEF2A mutations in coronary artery disease. J Clin Invest 115:1016–1020

    Article  PubMed  CAS  Google Scholar 

  45. Mayer B, Fischer M, Erdmann J, Holmer S, Lieb W, Hubauer U, Klein G, Nürnberg G, Nürnberg P, Löwel H, Broeckel U, Jacob H, Saar K, Reis A, Hengstenberg C, Schunkert H (2002) Identification of autosomal dominant heritability of myocardial infarction. Abstract, Circulation 105(Suppl)

  46. Assmann G, Cullen P, Schulte H (2002) Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study. Circulation 105:310–315

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Universitätsklinikum Schleswig-Holstein (UKSH), Ratzeburger Allee 160, Campus Lübeck, Medizinische Klinik II, 23538, Lübeck, Germany

    Björn Mayer MD, Jeanette Erdmann PhD & Heribert Schunkert MD

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  1. Björn Mayer MD
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Correspondence to Björn Mayer MD.

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Mayer, B., Erdmann, J. & Schunkert, H. Genetics and heritability of coronary artery disease and myocardial infarction. Clin Res Cardiol 96, 1–7 (2007). https://doi.org/10.1007/s00392-006-0447-y

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