Skip to main content
SpringerLink
Log in

The Genetic Challenge of Coronary Artery Disease

  • Chapter
  • First Online:
Clinical Approach to Sudden Cardiac Death Syndromes

  • 1191 Accesses

Abstract

Coronary artery disease (CAD) is a major health and economic problem for most of the world. In 2002, it accounted for one third of all the deaths in the world1 and is said to account for 38% of all deaths in the United States. Over thirteen million Americans experience CAD annually at a yearly cost of about four hundred billion dollars.2 Current epidemiological estimates suggest that at the time of birth, one can predict that, in their lifetime, they will have a 47% chance of experiencing a cardiac event and if combined with cerebrovascular disease more than 60%.3 The fundamental defect responsible for CAD is atherosclerosis which occurs in major blood vessels throughout the body, but the consequences are more devastating when it occurs in vessels that supply blood to organs such as the heart, brain, and kidney. The presence of coronary atherosclerosis with the superimposition of a thrombus can lead to the clinical manifestation of angina, myocardial infarction, and sudden cardiac death. CAD has long been the most common cause of death in the western world. It is rapidly increasing worldwide with the prediction of being number one killer in the world by 2010.2

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 149.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Heart Disease and Stroke Statistics - 2005 update. American Heart Association 2005

    Google Scholar 

  2. American Heart Association: Heart and Stroke Statistical Update. American Heart Association; 2000. Dallas, ed

    Google Scholar 

  3. Chaer RA, Billeh R, Massad MG. Genetics and gene manipulation therapy of premature coronary artery disease. Cardiology. 2004;101(1-3):122-130

    Article  PubMed  Google Scholar 

  4. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326:1419-1423

    Article  CAS  PubMed  Google Scholar 

  5. Chan L, Boerwinkle E. Gene-environment interactions and gene therapy in atherosclerosis. Cardiol Rev. 1994;2(3): 130-137

    Article  Google Scholar 

  6. Gertler M, White PD. Coronary Heart Disease in Young Adults: A Multidisciplinary Study.Cambridge: Harvard University Press; 1954

    Google Scholar 

  7. Lusis AJ, Mar R, Pajukanta P. Genetics of atherosclerosis. Annu Rev Genomics Hum Genet. 2004;5:189-218

    Article  CAS  PubMed  Google Scholar 

  8. Rose GC. Familial patterns in ischemic heart disease. Br J Prev Soc Med. 1964;(18):75-80

    Google Scholar 

  9. Rissanen A. Familial occurrence of coronary heart disease: effect of age at diagnosis. Am J Cardiol. 1979;44:60-66

    Article  CAS  PubMed  Google Scholar 

  10. Hamsten A, de Faire U. Risk Factors for coronary artery disease in families of young men with myocardial infarction. Am J Cardiol. 1987;59:14-19

    Article  CAS  PubMed  Google Scholar 

  11. ten Kate LP, Boman H, Daiger SP, et al. Familial aggregation of coronary heart disease and its relation to known genetic risk factors. Am J Cardiol. 1982;50:945-953

    Article  PubMed  Google Scholar 

  12. Sholtz RI, Rosenman RH, Brand RJ. The relationship of reported parental history to the incidence of coronary heart disease in the Western Collaborative Group Study. Am J Epidemiol. 1975;102:350-356

    CAS  PubMed  Google Scholar 

  13. Colditz GA, Rimm EB, Giovannucci E, et al. A prospective study of parental history of myocardial infarction and coronary artery disease in men. Am J Cardiol. 1991;67:933-938

    Article  CAS  PubMed  Google Scholar 

  14. Barrett-Connor E, Khaw K. Family history of heart attack as an independent predictor of death due to cardiovascular disease. Circulation. 1984;(69):1065-1069

    Google Scholar 

  15. Colditz GA, Stampfer MJ, Willett WC, et al. A prospective study of parental history of myocardial infarction and coronary heart disease in women. Am J Epidemiol. 1986;123: 48-58

    CAS  PubMed  Google Scholar 

  16. Schildkraut JM, Myers RM, Cupples LA, et al. Coronary risk associated with age and sex of parental heart disease in the Framingham Study. Am J Cardiol. 1989;64:555-559

    Article  CAS  PubMed  Google Scholar 

  17. Phillips AN, Sharper AG, Pocock SJ, et al. Parental death from heart disease and the risk of heart attack. Eur Heart J. 1988;9:243-251

    CAS  PubMed  Google Scholar 

  18. Hopkins PN, Williams RR, Kuida H, et al. Family history as an independent risk factor for incident coronary artery disease in a high-risk cohort in Utah. Am J Cardiol. 1988;62: 703-707

    Article  CAS  PubMed  Google Scholar 

  19. Adlersberg D, Parets AD, Boas EP. Genetics of atherosclerosis: studies of families with xanthoma and unselected patients with coronary artery disease under the age of fifty years. JAMA. 1949;141:246-254

    Google Scholar 

  20. Blumenthal S, Jesse MJ, Hennekens CH, et al. Risk factors for coronary artery disease in children of affected families. J Pediatr. 1975;87:1187-1192

    Article  CAS  PubMed  Google Scholar 

  21. Rissanen A, Nikkila EA. Identification of the high-risk groups in familial coronary heart disease. Br Heart J. 1977;39:875

    Google Scholar 

  22. Hamby RI. Hereditary aspects of coronary artery disease. Am Heart J. 1981;101:639-649

    Article  CAS  PubMed  Google Scholar 

  23. Berg KA, Dahlen G, Borresen AL. La(a) phenotypes, other lipoprotein parameters and a family history of coronary heart disease in middle-aged males. Clin Genet. 1979;16(5): 347-352

    Article  CAS  PubMed  Google Scholar 

  24. Becker DM, Becker L, Pearson TA, et al. Risk factors in siblings of people with premature coronary heart disease. J Am Coll Cardiol. 2004;12(1273):1280

    Google Scholar 

  25. Rosengren A, Wilhelmsen L, Eriksson E, et al. Lipoprotein (a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. Br Med J. 2004;301:1248-1251

    Article  Google Scholar 

  26. Anderson AJ, Loeffler RF, Barboriak JJ, et al. Occlusive coronary artery disease and parental history of myocardial infarction. Prev Med. 1979;8:419-428

    Article  CAS  PubMed  Google Scholar 

  27. Falconer DS. The inhertiance of liability to certain diseases estimated from the incidence among relatives. Ann Hum Genet. 1965;29:51-71

    Article  Google Scholar 

  28. Allen G, Harvald B, Shields JP. Measures of twin concordance. Acta Genet. 1967;17:475-481

    Google Scholar 

  29. Lloyd-Jones DM, Larson MR, Beiser A, et al. Lifetime risk of developing coronary heart disease. Lancet. 1999;353: 89-92

    Article  CAS  PubMed  Google Scholar 

  30. Nora JJ, Lortshcher RH, Spangler RD, et al. Genetic-epidemiologic study of early-onset ischemic heart disease. Circulation. 1980;(61):503-508

    Google Scholar 

  31. Goldstein J, Hobbs H, Brown M. Familial hypercholeserterolemia. In: Scriver C. Beaudet A, Sly W, Valle D (eds) The metabolic and molecular bases of inherited disease. Vol II. McGraw Hill, New York, pp. 2862-2913

    Google Scholar 

  32. Innerarity TL, Mahley RW, Weisgraber KH, et al Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolemia. J Lipid Res 1990:31;1337-1349

    Google Scholar 

  33. Kotowski, I.K. et al. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am. J. Hum. Genet. 2006:78;410-422

    Google Scholar 

  34. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: A HuGE Association Review. Am J Epidemiol. 2004;160(5): 421-429

    Article  PubMed  Google Scholar 

  35. Lusis AJ, Rotter JL, Sparkes RS. Genetic markers for studies of atherosclerosis and related risk factors. In: Lusis AJ, Rotter JL, Sparkes RS, eds. Molecular Genetics of Coronary Artery Disease. Candidate Genes and Processes in Atherosclerosis.New York: Karger; 1992:363-418

    Google Scholar 

  36. Breslow JL. Genetics of lipoprotein abnormalities associated with coronary artery disease susceptibility. Annu Rev Genet. 2000;34:233-254

    Article  CAS  PubMed  Google Scholar 

  37. Marian AJ, Brugada R, Roberts R. Cardiovascular diseases caused by genetic abnormalities. In: O’Rourke RA, Fuster V, Alexander RW, Roberts R, eds. Hurst’s The Heart - Manual of Cardiology. 12th ed. New York: McGraw Hill; 2007

    Google Scholar 

  38. Investing in our Future: Preventing Chronic Diseases in Canada. Chronic Disease Prevention Alliance of Canada 2003

    Google Scholar 

  39. Marian AJ, Roberts R. The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2001; 33(4):655-670

    Article  CAS  PubMed  Google Scholar 

  40. Goncalo A, Kwong-Hang Tam P, Bustamante C, Ostrander EA, Scherer SW, et al. Human Genome Variation 2006: emerging views on structural variation and large-scale SNP analysis. Nat Genet. 2007;39(2):153-155

    Article  Google Scholar 

  41. Hinds DA, Stuve LL, Nilsen GB, et al. Whole-genome patterns of common DNA variation in three human populations. Science. 2005;307:1072-1079

    Article  CAS  PubMed  Google Scholar 

  42. Iles MM. What can Genome-wide Association studies tell us about the genetics of common disease? PLoS Genetics. 2008;4(2):1-7

    Article  Google Scholar 

  43. Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs HH. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science. 2004;305(5685): 869-872

    Article  CAS  PubMed  Google Scholar 

  44. Peng B, Kemmel M. Simulations provide support for the common disease-common variant hypothesis. Genetics. 2007;175:763-776

    Article  CAS  PubMed  Google Scholar 

  45. Wang WY, Barratt B, Clayton DG, Todd JA. Genome-Wide Association Studies: theoretical and practical concerns. Nat Rev Genet. 2005;6:109-118

    Article  CAS  PubMed  Google Scholar 

  46. Hirshhorn JN, Daly MJ. Genome-wide association studies for common diseases and complex traits. Nat Rev Genet. 2005;6:95-108

    Article  Google Scholar 

  47. Pare G, Serre D, Brisson D, et al. Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol. Am Hum Genet. 2007;80(4):673-682

    Article  CAS  Google Scholar 

  48. Krushkal J, Xiong M, Ferrell RE, et al. Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation. Hum Mol Genet. 2005;7:1379-1383

    Article  Google Scholar 

  49. Heinonen P, Koulu M, Pesonen U, et al. Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects. J Clin Endocr Metab. 1999;84:2429-2433

    Article  CAS  PubMed  Google Scholar 

  50. Horikawa Y, Oda N, Cox NJ, et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet. 2000;26:163-175

    Article  CAS  PubMed  Google Scholar 

  51. Stone LM, Kahn SE, Fujimoto WY, et al. A variation at position -30 of the beta-cell glucokinase gene promoter is associated with reduced beta-cell function in middle-aged Japanese-American men. Diabetes. 2005;45:422-428

    Article  Google Scholar 

  52. Morgan TM, Krumholz HM, Lifton RP, Spertus JA. Non-validation of reported genetic risk factors for acute coronary syndrome in a large-scale replication study. JAMA. 2007;297(14):1551-1561

    Article  CAS  PubMed  Google Scholar 

  53. Helgadottir A, Manolescu A, Thorleifsson G, et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet. 2004;36(3): 233-239

    Article  CAS  PubMed  Google Scholar 

  54. Thomas DC, Haile RW, Duggan D. Recent developments in genomewide association scans: A workshop summary and review. Am J Hum Genet. 2005;77:337-345

    Article  CAS  PubMed  Google Scholar 

  55. Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996;273(5281): 1516-1517

    Article  CAS  PubMed  Google Scholar 

  56. Lander ES. The new genomics: global views of biology. Science. 1996;274:536-539

    Article  CAS  PubMed  Google Scholar 

  57. Kruglyak L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet. 1999;22:139-144

    Article  CAS  PubMed  Google Scholar 

  58. The International HapMap Consortium. The International HapMap Project. Science. 2003;426:789-796

    Google Scholar 

  59. Roberts R. “New Gains in Understanding Coronary Artery Disease”, Interview with Dr. Robert Roberts. Affymetrix Microarray Bull. 2007;3(2):1-4

    Google Scholar 

  60. Roberts R, Stewart AFR. Personalized medicine: a future prerequisite for the prevention of coronary artery disease. Am Heart J. 2006;4(3):222-227

    Article  Google Scholar 

  61. Zheng G, Friedlin B, Gastwirth JL. Comparison of robust tests for genetic association using case-control studies. In: IMS Lecture Notes, editor. Eric L. Lehmann Symposium 2006. IMS Lecture Notes-Monograph Series; 2nd. Ref Type: Sound Recording

    Google Scholar 

  62. Li Q, Zheng G, Li Z, et al. Efficient approximation of p-value of the maximum of correlated tests, with application to genome-wide association studies. Ann Hum Genet. 2008;72: 397-406

    Google Scholar 

  63. Sabatti C, Service S, Freimer N. False discovery rate in linkage and association genome screens for complex disorders. Genetics. 2003;162(2):829-833

    Google Scholar 

  64. Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308(5720):385-389

    Article  CAS  PubMed  Google Scholar 

  65. Sladek R, Rocheleau G, Rung J, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445(7130):881-885

    Article  CAS  PubMed  Google Scholar 

  66. Graham RR, Kozyrev SV, Baechler EC, et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet. 2006;38(5): 550-555

    Article  CAS  PubMed  Google Scholar 

  67. Amundadottir LT, Sulem P, Gudmundsson J, et al. A common variant associated with prostate cancer in European and African populations. Nat Genet. 2006;38(6): 652-658

    Article  CAS  PubMed  Google Scholar 

  68. Glazier AM, Nadeau J, Ajioka J. Finding genes that underlie complex traits. Science. 2002;298:2345-2349

    Article  CAS  PubMed  Google Scholar 

  69. McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on Chromosome 9 associated with coronary heart disease. Science. 2007;316:1488-1491

    Article  CAS  PubMed  Google Scholar 

  70. Helgadottir A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007; 316(5830):1491-1493

    Article  CAS  PubMed  Google Scholar 

  71. Wellcome Trust Case Consortium. Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature. 2007;447(7145):661-678

    Article  Google Scholar 

  72. Samani NJ, Erdmann J, Hall AS, et al. Genomewide association analysis of coronary artery disease. New Engl J Med. 2007;357(5):443-453

    Article  CAS  PubMed  Google Scholar 

  73. Broadbent HM, Peden JF, Lorkowski S, Goel A, Ongen H, Green F, et al. Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked, SNPs in the ANRIL locus on chromosome 9p. Hum Mol Genet. 2007;29: ddm352

    Google Scholar 

  74. Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res. 2007;67(8):3963-3969

    Article  CAS  PubMed  Google Scholar 

  75. Helgadottir A, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008;40(2): 217-224

    Google Scholar 

  76. Hinohara K, et al. Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations. J Hum Genet. 2008;53(4):357-359

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada, K1Y 4W7

    Robert Roberts

Authors
  1. Robert Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert Roberts .

Editor information

Editors and Affiliations

  1. Masonic Medical Research Laboratory, Bleecker St. 2150, Utica, 13501, U.S.A.

    Ramon Brugada

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag London

About this chapter

Cite this chapter

Roberts, R., Wells, G., Chen, L. (2010). The Genetic Challenge of Coronary Artery Disease. In: Brugada, R. (eds) Clinical Approach to Sudden Cardiac Death Syndromes. Springer, London. https://doi.org/10.1007/978-1-84882-927-5_23

Download citation

  • DOI: https://doi.org/10.1007/978-1-84882-927-5_23

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84882-926-8

  • Online ISBN: 978-1-84882-927-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation