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Genetik der koronaren Herzkrankheit und des Herzinfarkts

Von der positiven Familienanamnese zum Gen

Genetics of coronary heart disease and myocardial infarction

From positive family history to the gene

Zusammenfassung

Aufgrund der hohen Prävalenz der koronaren Herzkrankheit (KHK) und des Herzinfarkts lassen sich in den Anamnesegesprächen oft familiäre Häufungen eruieren. Für die Risikostratifizierung ist es hierbei entscheidend, zwischen sporadischen Fällen und solchen mit „echter“ familiärer Häufung zu unterscheiden. Von einer familiären Prädisposition wird dann ausgegangen, wenn mindestens ein männlicher Verwandter 1. Grades vor dem 55. oder eine weibliche Verwandte 1. Grades vor dem 65. Lebensjahr einen Herzinfarkt erlitten haben oder eine KHK mit signifikanter Stenosierung diagnostiziert wurde. Die aktuelle Übersichtsarbeit möchte wesentliche Studien aufgreifen, aus denen sich das familiäre Risiko für die KHK und den Herzinfarkt ableitet. Darüber hinaus soll ein kurzer Überblick über den aktuellen Stand der genetischen Forschung zu KHK und Herzinfarkt gegeben werden.

Abstract

Because of their high prevalence, cases of coronary artery disease (CAD) and myocardial infarction (MI) are frequently found when asking for a patient’s family history. It is common knowledge that a positive familial history constitutes a risk factor for CAD in its own right, in addition to smoking, increased alcohol intake, diabetes, obesity, hypertension, and hyperlipidemia. Nevertheless, for correct risk assessment it is crucial to accurately distinguish between sporadic and true familial cases of CAD and MI. Familial disposition is present when at least one male first-grade relative under the age of 55 or one female first-grade relative under the age of 65 has/had been diagnosed with myocardial infarction or significant coronary artery disease. In the review presented here, we compile the relevant epidemiological and genetic studies that constitute the scientific basis of this risk assessment. Furthermore, a short overview of the state of the art of genetic CAD/MI research is given.

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Literatur

  1. 1.

    Andresdottir MB, Sigurdsson G, Sigvaldason H et al. (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 

  2. 2.

    Boer JM, Feskens EJ, Kuivenhoven JA et al. (2001) Parental history of myocardial infarction: lipid traits, gene polymorphisms and lifestyle. Atherosclerosis 155: 149–156

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Broeckel U, Hengstenberg C, Mayer B et al. (2002) A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet 30: 210–214

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Cambien F, Poirier O, Lecerf L et al. (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 15: 641–644

    Article  Google Scholar 

  5. 5.

    Couzin J, Kaiser J (2007) Genome-wide association. Closing the net on common disease genes. Science 316: 820–822

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Fischer M, Broeckel U, Holmer S et al. (2005) Distinct heritable patterns of angiographic coronary artery disease in families with myocardial infarction. Circulation 111: 855–862

    PubMed  Article  Google Scholar 

  7. 7.

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

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Helgadottir A, Manolescu A, Helgason A et al. (2006) A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet 38: 68–74

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Helgadottir A, Thorleifsson G, Manolescu A et al. (2007) A common variant on chromosome 9p21 Affects the risk of myocardial infarction. Science 8: 1491–1493

    Article  Google Scholar 

  10. 10.

    Hengstenberg C, Holmer SR, Mayer B et al. (2001) Siblings of myocardial infarction patients are overlooked in primary prevention of cardiovascular disease. Eur Heart J 22: 926–933

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Horne BD, Camp NJ, Muhlestein JB et al. (2006) Identification of excess clustering of coronary heart diseases among extended pedigrees in a genealogical population database. Am Heart J 152: 305–311

    PubMed  Article  Google Scholar 

  12. 12.

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

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    McPherson R, Pertsemilidis A, Kavaslar M et al. (2007) A common allele on chromosome 9 associated with coronary heart disease. Science 316: 1488

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Morgan TM, Krumholz HM, Lifton RP et al. (2007) Nonvalidation of reported genetic risk factors for acute coronary syndrome in a large-scale replication study. JAMA 297: 1551–1561

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Murabito JM, Pencina MJ, Nam BH et al. (2005) Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults. JAMA 294: 3117–3123

    PubMed  Article  CAS  Google Scholar 

  16. 16.

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

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Samani NJ, Erdmann J, Hall AS (2007) Genome-wide association analysis of coronary artery disease. N Engl J Med in press

  18. 18.

    Topol EJ, Smith J, Plow EF et al. (2006) Genetic susceptibility to myocardial infarction and coronary artery disease. Hum Mol Genet 2: R117–123

    Article  Google Scholar 

  19. 19.

    Tunstall-Pedoe H, Vanuzzo D, Hobbs M et al. (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

    PubMed  Article  CAS  Google Scholar 

  20. 20.

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

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661–678

    Article  Google Scholar 

  22. 22.

    Wichmann HE, Gieger C, Illig T et al. (2005) KORA-gene – resource for population genetics, controls and a broad spectrum of disease phenotypes. Gesundheitswesen [Suppl 1] 67: S26–30

  23. 23.

    Yusuf S, Hawken S, Ounpuu S et al. (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364: 937–952

    PubMed  Article  Google Scholar 

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Correspondence to J. Erdmann .

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Erdmann , J., Schunkert, H. Genetik der koronaren Herzkrankheit und des Herzinfarkts. medgen 19, 316–320 (2007). https://doi.org/10.1007/s11825-007-0029-z

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Schlüsselwörter

  • Koronare Herzkrankheit
  • KHK
  • Herzinfarkt
  • Familiäre Prädisposition
  • Genetische Forschung

Keywords

  • Coronary artery disease
  • CAD
  • Myocardial infarction
  • Familial disposition
  • Genetic CAD/MI research