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Clinical Applications of Bioinformatics, Genomics, and Pharmacogenomics

  • Protocol
Bioinformatics and Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 316))

Abstract

Elucidation of the entire human genomic sequence is one of the greatest achievements of science. Understanding the functional role of 30,000 human genes and more than 2 million polymorphisms was possible through a multidisciplinary approach using microarrays and bioinformatics. Polymorphisms, variations in DNA sequences, occur in 1% of the population, and a vast majority of them are single nucleotide polymorphisms. Genotype analysis has identified genes important in thrombosis, cardiac defects, and risk of cardiac disease. Many of the genes show a significant correlation with polymorphisms and the incidence of coronary artery disease and heart failure. In this chapter, the application of current state-of-the-art genomic analysis to a variety of these disorders is reviewed.

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References

  1. Department of Health and Human Services, National Institutes of Health. (2000) Disease-specific estimates of direct and indirect costs of illness and NIH support, and HHS and National Costs for 13 Diseases and Conditions (House Report 106-370), February, 2000.

    Google Scholar 

  2. Silverstein, M. D., Heit, J. A., Mohr, D. N., Petterson, T. M., O’Fallon, W. M., and Melton, L. J. (1998) Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch. Intern. Med. 158, 585–593.

    Article  PubMed  CAS  Google Scholar 

  3. Rosendal, F. R. (1999) Venous thrombosis: a multicausal disease. Lancet 353, 1167–1173.

    Article  Google Scholar 

  4. McCarthy, J. J. and Hilfiger, R. (2000) The use of single nucleotide polymorphisms maps in pharmacogenomics. Nat. Biotechnol. 18, 505–508.

    Article  PubMed  CAS  Google Scholar 

  5. Krynetski, E. Y. and Evans, W. E. (1999) Pharmacogenetics as a molecular basis of individualized drug therapy: the thiopurine-S-methyltransferase paradigm. Pharm. Res. 16, 342–349.

    Article  PubMed  CAS  Google Scholar 

  6. Drazen, J. M., Yandava, C. N., Dube, L., et al. (1999) Pharmacogenetic association between ALOX5 promoter genotype and the response to asthma treatment. Nat. Genet. 22, 168–170.

    Article  PubMed  CAS  Google Scholar 

  7. Collins, F. S. (1992) Positional cloning: let’s not call it reverse anymore. Nat. Genet. 1, 3–6.

    Article  PubMed  CAS  Google Scholar 

  8. Chasman, D. and Adams, R. M. (2001) Predicting the functional consequences of nonsynonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. J. Mol. Biol. 307, 683–706.

    Article  PubMed  CAS  Google Scholar 

  9. Humphries, S. E., Ye, S., Talmud, P., Bara, L., Wilhelmsen, L., and Tiret, L. (1995) European Atherosclerosis Research Study: genotype at the fibrinogen locus (G-455-Aβ-gene) is associated with differences in plasma fibrinogen levels in young men and women from different regions in Europe: evidence for gender-genotype environment interaction. Arterioscler Thromb. Vasc. Biol. 15, 96–104.

    PubMed  CAS  Google Scholar 

  10. Nishiuma, S., Kario, K., Yakushijin, K., et al. (1998) Genetic variation in the promoter of the β-fibrinogen gene is associated with ischemic stroke in a Japanese population. Blood Coagulation Fibrinolysis 9, 373–379.

    Article  PubMed  CAS  Google Scholar 

  11. Muzbeck, L., Adany, R., and Mikkola, H. (1996) Novel aspects of blood coagulation Factor XIII. I. Structure, distribution, activation and function. Crit. Rev. Clin. Lab. Sci. 33, 357–421.

    Article  Google Scholar 

  12. De Backer, G., De Henauw, S., Sans, S., et al. (1999) A comparison of lifestyle, genetic, bioclinical and biochemical variables of offspring with and without family histories of premature coronary heart disease: the experience of the European Atherosclerosis Research Studies. J. Cardiovasc. Risk 6, 183–188.

    PubMed  Google Scholar 

  13. Carter, A. M., Mansfield, M. W., Strickland, M. H., and Grant, P. J. (1996) Beta-fibrinogen gene-455 G/A polymorphism and fibrinogen levels: risk factors for coronary artery disease in subjects with NIDDM. Diabetes Care 19, 1265–1268.

    Article  PubMed  CAS  Google Scholar 

  14. Carter, A. M., Ossei-Gerning, N., Wilson, I. J., and Grant, P. J. (1997) Association pf the platelet P(A) polymorphism of the glycoprotein Iib/IIIa and the fibrinogen Bbeta 448 polymorphism with myocardial infarction and extent of coronary artery disease. Circulation 96, 1424–1431.

    PubMed  CAS  Google Scholar 

  15. Gensini, G. F., Comeglio, M., and Colella, A. (1998) Classical risk factors and emerging elements in the risk profile for coronary artery disease. Eur. Heart J. 19(Suppl. A), A53–A61.

    PubMed  Google Scholar 

  16. Schmidt, H., Schmidt, R., Niederkorn, K., et al. (1998) Beta-fibrinogen gene polymorphism (C148✦T) is associated with carotid atherosclerosis: results of the Austrian Stroke Prevention Study. Arterioscler. Thromb. Vasc. Biol. 18, 487–492.

    PubMed  CAS  Google Scholar 

  17. Kessler, C., Spitzer, C., Strauske, D., et al. (1997) The apolipoprotein E and beta-fibrinogen G/A-455 gene polymorphism are associated with ischemic stroke involving the large vessel disease. Arterioscler. Thromb. Vasc. Biol. 17, 2880–2884.

    PubMed  CAS  Google Scholar 

  18. de Maat, M. P., Kastelein, J. J., Jukema, J. W., et al. (1998) ™455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: proposed role for an acute-phase reaction pattern of fibrinogen. REGRESS group. Arterioscler. Thromb. Vasc. Biol. 18, 265–271.

    PubMed  Google Scholar 

  19. Behague, I., Poirier, O., Nicaud, V., et al. (1996) Beta fibrinogen gene polymorphisms are associated with plasma fibrinogen and coronary artery disease in patients with myocardial infarction. The ECTIM Study: Etude Cas-Temoins sur l’Infarctus du Myocarde. Circulation 93, 440–449.

    PubMed  CAS  Google Scholar 

  20. Wang, X. L., Wang, J., McCredie, R. M., and Wilcken, D. E. (1997) Polymorphisms of factor V, factor VII, and fibrinogen genes: relevance to severity of coronary artery disease. Arterioscler. Thromb. Vasc. Biol. 17, 246–251.

    PubMed  CAS  Google Scholar 

  21. Poort, S. R., Rosendaal, F. R., Reitsma, P. H., and Bertina, R. M. (1996) A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88, 3698–3703.

    PubMed  CAS  Google Scholar 

  22. Hillarp, A., Zoller, B., Svenson, P. J., and Dahlback, B. (1997) The 20210 allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified venous thrombosis. Thromb. Haemost. 78, 990–992.

    PubMed  CAS  Google Scholar 

  23. Rosendaal, F. R., Siscovick, D. S., Schwartz, S. M., Psaty, B. M., Raghunathan, T. E., and Vos, H. L. (1997) A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 90, 1747–1750.

    PubMed  CAS  Google Scholar 

  24. Ferraresi, P., Marchetti, G., Legnani, C., et al. (1997) The heterozygous 20210 G/A prothrombin genotype is associated with early venous thrombosis in inherited thrombophilias and is not increased in frequency in artery disease. Arterioscler. Thromb. Vasc. Biol. 17, 2418–2422.

    PubMed  CAS  Google Scholar 

  25. Zoller, B., Svensson, P. J., Dhalback, B., and Hillarp, A. (1998) The 20210 allele of prothrombin gene is frequently associated with the factor V Arg 506 to Gln mutation is not with protein S deficiency in thrombophilic families. Blood 91, 2209–2211.

    Google Scholar 

  26. Ehrenforth, S., Ludwig, G., Klinke, S., Krause, M., Scharre, I., and Nowak-Gottl, U. (1998) The prothrombin 20210 A allele is frequently coinherited in young carriers of the factor B Arg 506 to Gln mutation with venous thrombophilia. Blood 91, 2209, 2210.

    PubMed  Google Scholar 

  27. Howard, T. E., Marusa, M., Boisza, J., et al. (1998) The prothrombin gene 3′-untranslated region mutation is frequently associated with factor V Leiden in thrombophilic patients and shows ethnic specific variation in allele frequency. Blood 91, 1092.

    PubMed  CAS  Google Scholar 

  28. Silver, D. and Vouyouka, A. (2000) The Caput medusae of hypercoagulability. J. Vasc. Surg. 31, 396–405.

    Article  PubMed  CAS  Google Scholar 

  29. Manoussakis, M. N., Tziofas, A. G., Silis, M. P., Pange, P. J., Goudevenous, J., and Moutsopoulos, H. M. (1987) High prevalence of anti-cardiolipin and other autoantibodies in a healthy elderly population. Clin. Exp. Immunol. 69, 557–565.

    PubMed  CAS  Google Scholar 

  30. Lechner, K. and Pabinger-Fasching, I. (1985) Lupus anticoagulant and thrombosis: a study of 25 cases and review of the literature. Haemostasis 15, 254–262.

    PubMed  CAS  Google Scholar 

  31. Manucci, P. M. (2000) The molecular basis of inherited thrombophilia. Vox. Sang. 78(Suppl. 2), 39–45.

    PubMed  CAS  Google Scholar 

  32. Foka, Z. J., Lambropoulos, A. F., Saravelos, H., et al. (2000) Factor V Leiden and prothrombin G20210 mutations but no methylenetetrahydrofolate reductase C677T are associated with recurrent miscarriages. Hum. Reprod. 15, 458–462.

    Article  PubMed  CAS  Google Scholar 

  33. Amitrano, L., Brancaccio, V., Guardascione, M. A., et al. (2000) Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology 31, 345–348.

    Article  PubMed  CAS  Google Scholar 

  34. Ekberg, H., Svensson, P. J., Simanaiteis, M., and Dahlback, B. (2000) Factor V R506q mutation (activated protein C resistance) is additional risk factor for early renal graft loss associated with acute vascular rejection. Transplantation 69, 1577–1581.

    Article  PubMed  CAS  Google Scholar 

  35. Rees, D. C., Cox, M., and Clegg, J. B. (1995) World distribution of Factor V Leiden. Lancet 346, 1133–1134.

    Article  PubMed  CAS  Google Scholar 

  36. Iacovelli, L., Di Castelnuovo, A., de Knijiff, P., et al. (1996) Alu-repeat polymorphism in the tissue-type plasminogen activator (tPA) gene, tPA levels and risk of familial myocardial infarction (MI). Fibrinolysis 10, 13–16.

    Article  Google Scholar 

  37. Furie, B. and Burie, B. C. (1992) Molecular and cellular biology of blood coagulation. N. Engl. J. Med. 326, 800–806.

    Article  PubMed  CAS  Google Scholar 

  38. Wartiovaara, U., Mikkola, H., Szoke, G., et al. (2000) Effect of Val34Leu polymorphism on the activation of the coagulation Factor XIIIa. Thromb. Haemost. 84, 595–600.

    PubMed  CAS  Google Scholar 

  39. Ariens, R. A. S., Philippou, H., Nagaswami, C., Weisel, J. W., Lane, D. A., and Grant, P. J. (2000) The Factor XIII V34L polymorphism accelerates thrombin activation of Factor XIII and affects crosslinked fibrin structure. Blood 96, 988–995.

    PubMed  CAS  Google Scholar 

  40. Kohler, H. P., Stickland, M. H., Ossei-Gernig, N., Carter, A., Mikkola, H., and Grant, P. J. (1998) Association of a common polymorphism in the Factor XIII gene with myocardial infarction. Thromb. Haemost. 79, 8–13.

    PubMed  CAS  Google Scholar 

  41. Wartiovaara, U., Perola, M., Mikkola, H., et al. (1999) Association of Factor XIII Va34Leu with decrease risk of myocardial infarction in Finnish males. Atherosclerosis 142, 295–300.

    Article  PubMed  CAS  Google Scholar 

  42. Doggen, C. J. M., Kunz, G., Rosebdaal, F. R., et al. (1998) A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr and the risk of myocardial infarction in men. Thromb. Haemost. 80, 743–748.

    PubMed  CAS  Google Scholar 

  43. Li, Y. H., Chen, J. H., Wu, H. L., et al. (2000) G-33A mutation in the promoter region of thrombomodulin gene and its association with coronary artery disease and plasma soluble thrombomodulin levels. Am. J. Cardiol. 85, 8–12.

    Article  PubMed  CAS  Google Scholar 

  44. Li, Y. H., Chen, C. H., Yeh, P. S., et al. (2001) Functional mutation in the promoter region of thrombomodulin gene in relation to carotid atherosclerosis. Atherosclerosis 154, 713–719.

    Article  PubMed  CAS  Google Scholar 

  45. Kleesiek, K., Schmidt, M., Gotting, C., Brinkman, T., and Prohaska, W. (1998) A first mutation in the human tissue factor pathway inhibitor gene encoding [P151L] TFPI. Blood 92, 3976–3977.

    PubMed  CAS  Google Scholar 

  46. Moatti, D., Seknadji, P., Galand, C., et al. (1999) Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with acute coronary syndromes and in healthy subjects: impact of the V264M substitution on plasma levels of TFPI. Arterioscler. Thromb. Vasc. Biol. 19, 862–869.

    PubMed  CAS  Google Scholar 

  47. Kleesiek, K., Schmidt, M., Gotting, C., et al. (1999) The 536C✦T transition in the human tissue factor pathway inhibitor (TFPI) gene is statistically associated with a higher risk for venous thrombosis. Thromb. Haemost. 82, 1–5.

    PubMed  CAS  Google Scholar 

  48. Moatti, D., Haidar, B., Fumeron, F., et al. (2000) A new T-287C polymorphism in the 5′ regulatory region of the tissue factor pathway inhibitor gene: association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels. Thromb. Haemost. 84, 244–249.

    PubMed  CAS  Google Scholar 

  49. Ameziane, N., Seguin, C., Borgel, D., et al. (2002) The −33T✦C polymorphism in intron 7 of the TFPI gene influences the risk of venous thromboembolism: independently of the Factor V Leiden and prothrombin mutations. Thromb. Haemost. 88, 195–199.

    PubMed  CAS  Google Scholar 

  50. Merati, G. B., Biguzzi, F., Oganesyan, N., et al. (1999) A 23bp insertion in the endothelial protein C receptor (EPCR) gene in patients with myocardial infarction in deep vein thrombosis. Thromb. Haemost. 82, 507.

    Google Scholar 

  51. Brattstrom, L., Isrealsson, B., Norrving, B., et al. (1990) Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment. Atherosclerosis 81, 51–60.

    Article  PubMed  CAS  Google Scholar 

  52. Dudman, N. P., Wilcken, D. E., Wang, J., et al. (1993) Disordered methionine/homocysteine metabolism in premature vascular disease: its occurrence, cofactor therapy and enzymology. Arterioscler. Thromb. 13, 1253–1260.

    PubMed  CAS  Google Scholar 

  53. Boers, G. H. (1989) Carriership for momocystinuria in juvenile vascular disease. Haemostasis 19(Suppl. 1), 29–34.

    PubMed  Google Scholar 

  54. Brattstrom, L. E., Hardebo, J. E., and Hultberg, B. L. (1984) Moderate homocysteinemia —a possible risk factor for arteriosclerotic cerebrovascular disease. Stroke 15, 1012–1016.

    PubMed  CAS  Google Scholar 

  55. Bienvenu, T., Ankri, A., Chadefaux, B., et al. (1993) Elevated total plasma homocyteine, a risk factor for thrombosis: relation to coagulation and fibrinolytic parameters. Thromb. Res. 70, 123–129.

    Article  PubMed  CAS  Google Scholar 

  56. Florell, S. R. and Rodgers, G. M. (1997) Inherited thrombotic disorders: an update. Am. J. Haematol. 54, 53–60.

    Article  CAS  Google Scholar 

  57. Simioni, P., Prandoni, P., Burlina, A., et al. (1996) Hyperhomocystinemia and deep vein thrombosis: a case-control study. Thromb. Haemost. 76, 883–886.

    PubMed  CAS  Google Scholar 

  58. Selhub, J., Jaques, P. F., Wilson, P. W., et al. (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270, 2693–2698.

    Article  PubMed  CAS  Google Scholar 

  59. Afshar-Kharghan, V., Khoshnevis-Als, M., and Lopez, J. (1999) A Kozak sequence polymorphism is a major determinant of the surface levels of a platelet adhesion receptor. Blood 94(1), 186–191.

    Google Scholar 

  60. Anderson, J. L., King, G. J., Bair, T. L., et al. (1999) Associations between a polymorphism in the gene encoding of glycoprotein IIIa gene in patients with coronary artery disease. J. Am. Coll. Cardiol. 33, 727–733.

    Article  PubMed  CAS  Google Scholar 

  61. Garcia-Ribes, M., Gonzales-Lamuno, D., Hernandez-Estefania, R., et al. (1998) Polymorphism of the platelet glycoprotein IIIa gene in patients with coronary stenosis. Thromb. Haemost. 79, 1126–1129.

    PubMed  CAS  Google Scholar 

  62. Kastrati, A., Schomig, A., Seyfarth, M., et al. (1999) PIA polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement. Circulation 99, 1005–1010.

    PubMed  CAS  Google Scholar 

  63. Goldmuntz, E., Clark, B. J., Mitchell, L. E., et al. (1998) Frequency of 22q11 deletions in patients with conotruncal defects. J. Am. Coll. Cardiol. 32, 492–498.

    Article  PubMed  CAS  Google Scholar 

  64. Momma, K., Kondo, C., Matsuoka, R., and Tkao, A. (1996) Cardiac anomalies associated with a chromosome 22q11 deletion in patients with conotruncal anomaly face syndrome. Am. J. Cardiol. 78, 591–594.

    Article  PubMed  CAS  Google Scholar 

  65. Seaver, L. H., Pierpont, J. W., Erickson, R. P., et al. (1994) Pulmonary atresia associated with maternal 22q11.2 deletion: possible parent of origin effect in the conotruncal anomaly face syndrome. J. Med. Genet. 31, 830–834.

    Article  PubMed  CAS  Google Scholar 

  66. Hofbeck, M., Rauch, A., Buheitel, G., et al. (1998) Monosomy 22q11 in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. Heart 79, 180–185.

    PubMed  CAS  Google Scholar 

  67. Hubert, R. S., Mitchell, S., Chen, X. N., et al. (1997) BAC and PAC contigs covering 3.5 Mb of the Down syndrome congenital heart disease region between D21S55 and MX1 on chromosome 21. Genomics 41, 218–226.

    Article  PubMed  CAS  Google Scholar 

  68. Korenberg, J. R., Bradley, C., and Disteche, C. M. (1992) Down syndrome: molecular mapping of the congenital heart disease and duodenal stenosis. Am. J. Hum. Genet. 50, 294–302.

    PubMed  CAS  Google Scholar 

  69. Nadal, M., Mila, M., Pritchard, M., et al. (1996) YAC and cosmid FISH mapping of an unbalanced chromosomal translocation causing partial trisomy 21 and Down’s syndrome. Hum. Genet. 98, 460–466.

    Article  PubMed  CAS  Google Scholar 

  70. Del Rio, T., Urban, Z., Csiszar, K., and Boyd, C. D. (1998) A gene-dosage PCR method for the detection of elastin gene deletions in patients with Williams syndrome. Clin. Genet. 54, 129–135.

    Article  PubMed  Google Scholar 

  71. Urban, Z., Kiss, E., Kadar, K., et al. (1997) Genetic diagnosis of Williams syndrome. Orvi.Hetil. 138, 1749–1752.

    CAS  Google Scholar 

  72. Tynan, K., Comeau, K., Pearson, M., et al. (1993) Mutation screening of complete fibrillin-1 coding sequence: report of five new mutations, including two in 8-cysteine domains. Hum. Mol. Genet. 2, 1813–1821.

    Article  PubMed  CAS  Google Scholar 

  73. Rossi, G. P., Cesari, M., Zanchetta, M., Colonna, S., et al. (2003) The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the Genica study. J. Am. Coll. Cardiol. 41, 930–937.

    Article  PubMed  CAS  Google Scholar 

  74. Linder, L., Kiowski, W., Buhler, F. R., and Luscher, T. F. (1990) Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo: blunted response in essential hypertension. Circulation 81, 1762–1767.

    PubMed  CAS  Google Scholar 

  75. Celemajer, D. S., Sorensen, K. E., Spiegelhalter, D. J., et al. (1994) Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J. Am. Coll. Cardiol. 24, 471–476.

    Article  Google Scholar 

  76. Luscher, T. F., Tanner, F. C., Tschudi, M. R., et al. (1993) Endothelial dysfunction in coronary artery disease. Annu. Rev. Med. 44, 395–418.

    Article  PubMed  CAS  Google Scholar 

  77. Al Suwaidi, J., Hamasaki, S., Higano, S. T., et al. (2000) Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 101, 848–854.

    Google Scholar 

  78. Huang, P. L., Huang, Z., Mashimo, H., et al. (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377, 239–242.

    Article  PubMed  CAS  Google Scholar 

  79. Shesely, E. G., Maeda, N., Kim, H. S., et al. (1996) Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc. Natl. Acad. Sci. USA 93, 13,176–13,181.

    Article  PubMed  CAS  Google Scholar 

  80. Aji, W., Ravalli, S., Szabolcs, M., et al. (1997) L-Arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice. Circulation 95, 430–437.

    PubMed  CAS  Google Scholar 

  81. Feng, Q., Song, W., Lu, X., et al. (2002) Development of heart failure and congenital septal defects in mice lacking endothelial nitric oxide synthase. Circulation 106, 873–879.

    Article  PubMed  CAS  Google Scholar 

  82. Ishizuka, T., Takamizawa-Matsumoto, M., Suzuki, K., et al. (1999) Endothelin-1 enhances vascular cell adhesion molecule-1 expression in tumour necrosis factor alpha-stimulated vascular endothelial cells. Eur. J. Pharmacol. 369, 237–245.

    Article  PubMed  CAS  Google Scholar 

  83. Rossi, G. P., Seccia, T. M., and Nussdorfer, G. G. (2001) Reciprocal regulation of endothelin-1 and nitric oxide: relevance in the physiology and pathology of the cardiovascular system. Int. Rev. Cytol. 209, 241–272.

    Article  PubMed  CAS  Google Scholar 

  84. Ross, R. (1999) Atherosclerosis—an inflammatory disease. Nature 340, 115–126.

    CAS  Google Scholar 

  85. Ohashi, Y., Kawashima, S., Hirata, K., et al. (1998) Hypertension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase. J. Clin. Invest. 102, 2061–2071.

    Article  PubMed  CAS  Google Scholar 

  86. Rossi, G. P., Taddei, S., Virdis, A., et al. (2003) The T-786 and Glu298 Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of the Caucasian hypertensive patients. J. Am. Coll. Cardiol. 41, 838–845.

    Google Scholar 

  87. Goldstein, J. L., Hobbs, H. H., and Brown, M. S. (2001) Familial hypercholesterolemia, in The Metabolic & Molecular Bases of Inherited Disease, 8th ed., vol. 2 (Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds.), McGraw-Hill, New York, pp. 2863–2913.

    Google Scholar 

  88. Kane, J. P. and Havel, R. J. (2001) Disorders of the biogenesis and secretion of lipoproteins containing the B apolipoprotein, in The Metabolic & Molecular Bases of Inherited Diseases, 8th ed., vol. 2. (Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds.), McGraw-Hill, New York, pp. 2717–2752.

    Google Scholar 

  89. Berge, K. E., Tian, H., Graf, G. A., et al. (2001) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290, 1771–1775.

    Article  Google Scholar 

  90. Lee, M. H., Lu, K., Hazzard, S., et al. (2001) Identification of a gene, ABCG5, important in the regulation dietary cholesterol absorption. Nat. Genet. 27, 79–83.

    Article  PubMed  CAS  Google Scholar 

  91. Cahilly, C., Ballantyne, C. M., Elghannam, H., Gotto, A. M., and Marlan, A. J. (2000) Novel polymorphisms in promoter region of ATP binding cassette transporter gene and plasma lipids, severity, progression and regression of coronary atherosclerosis. Circ. Res. 86, 391–395.

    PubMed  CAS  Google Scholar 

  92. Marian, A. J. and Roberts, R. (2003) Molecular genetics of cardiovascular disorders, in Evidence-Based Cardiology, 2nd ed. (Yousef, S., Cairns, J. A., Camm, A. J., Fallen, E. L., Gersh, B. J., and Books, B. M. J., eds.), BMA House, London, UK.

    Google Scholar 

  93. NHLBI Morbidity and Mortality Chartbook, 2002. National Heart, Lung, and Blood Institute, Bethesda, MD, May 2002 (http://www.nhlbi.nih.gov/resources/cht-book.htm).

  94. Geller, D. S., Farhi, A., and Pinkerton, C. A. (2000) Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science 289, 119–223.

    Article  PubMed  CAS  Google Scholar 

  95. Nabel, E. G. (2003) Cardiovascular disease. N. Engl. J. Med. 349, 60–72.

    Article  PubMed  CAS  Google Scholar 

  96. Maron, B. J., Shirani, J., Poliac, L. C., Mathenge, R., Roberts, W. C., and Mueller, F. O. (1996) Sudden death in young competitive athletes. Clinical, demographic and pathological profiles. JAMA 276, 199–204.

    Article  PubMed  CAS  Google Scholar 

  97. Maron, B. J., Anan, T. J., and Roberts, W. C. (1981) Quantitative analysis of the distribution of cardiac muscle cell disorganization in the left ventricular wall of patients with hypertrophic cardiomyopathy. Circulation 63, 882–894.

    PubMed  CAS  Google Scholar 

  98. Tiso, N., Stephan, D. A., Nava, A., et al. (2001) Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum. Mol. Genet. 10, 189–194.

    Article  PubMed  CAS  Google Scholar 

  99. Bennett, P. B., Yazawa, K., Makita, N., and George, A. L. Jr. (1995) Molecular mechanism for an inherited cardiac arrhythmia. Nature 376, 683–685.

    Article  PubMed  CAS  Google Scholar 

  100. Wang, Q., Shen, J., Splawski, I., et al. (1995) SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80, 805–811.

    Article  PubMed  CAS  Google Scholar 

  101. Chen, Q., Kirsch, G. E., Zhang, D., et al. (1998) Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 392, 293–296.

    Article  PubMed  CAS  Google Scholar 

  102. Schott, J. J., Alshinawi, C., Kyndt, F., et al. (1999) Cardiac conduction defects associate with mutations in SCN5A. Nat. Genet. 23, 20–21.

    Article  PubMed  CAS  Google Scholar 

  103. Tan, H. L., Bink-Boelkens, M. T., Bezzina, C. R., et al. (2001) A sodium channel mutation causes isolated cardiac conduction disease. Nature 409, 1043–1047.

    Article  PubMed  CAS  Google Scholar 

  104. Splawski, I., Shen, J., Timothy, K. W., et al. (2000) Spectrum of mutations in long QT syndrome genes: KVLQT1, HERG, SCN5A, KCNE1 and KCNE2. Circulation 102, 1178–1185.

    PubMed  CAS  Google Scholar 

  105. Fiala, M., Popik, W., Roos, K., Cashman, J., and Arthos, J. (2003) Molecular pathogenesis of HIV cardiomyopathy and drug-induced heart disease, in From Genome to Disease: A Symposium of High Throughput Biology.

    Google Scholar 

  106. Sousa, J. E., Costa, M. A., Abizaid, A., et al. (2001) Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative angiography and three dimensional intravascular ultrasound study. Circulation 103, 192–195.

    PubMed  CAS  Google Scholar 

  107. Roberts, R. (2000) A perspective: the new millennium dawns on a new paradigm for cardiology—molecular genetics. J. Am. Coll. Cardiol. 36, 661–667.

    Article  PubMed  CAS  Google Scholar 

  108. NHLBI Factbook, Fiscal Year 2002. National Heart, Lung and Blood Institute, Bethesda, MD, February 2003 (http://www.nhlbi.nih.gov/about/factpdf.htm.).

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Author information

Authors and Affiliations

  1. Department of Pathology, Loyola University Medical Center, Maywood, IL

    Omer Iqbal & Jawed Fareed

Authors
  1. Omer Iqbal
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  2. Jawed Fareed
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Editors and Affiliations

  1. Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM

    Richard S. Larson

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© 2006 Humana Press Inc.

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Iqbal, O., Fareed, J. (2006). Clinical Applications of Bioinformatics, Genomics, and Pharmacogenomics. In: Larson, R.S. (eds) Bioinformatics and Drug Discovery. Methods in Molecular Biology, vol 316. Humana Press. https://doi.org/10.1385/1-59259-964-8:159

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  • DOI: https://doi.org/10.1385/1-59259-964-8:159

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-346-6

  • Online ISBN: 978-1-59259-964-6

  • eBook Packages: Springer Protocols

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