Abstract
Atherosclerosis, the cause of coronary artery disease (CAD) and stroke, is in reality not one disease but many different diseases, each with a similar endpoint (vascular lesions) but differing in genetic and environmental contributions. In genetic terms, atherosclerosis is very “heterogeneous.” Within particular populations, genetic differences appear to be of primary importance in determining who will develop atherosclerosis, and its consequent clinical sequelae, and who will not. Between populations, particularly between those populations consuming different levels of dietary fat, environmental influences predominate.
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References
Anonymous. Mouse Genome Database. Mouse Genome Informatics Project, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web.(URL:http://www.informatics.jax.org), 1995.
Anonymous. GDB(TM) Human Genome Data Base. Johns Hopkins University, Baltimore, Maryland. World Wide Web. (URL:http://gdbwww.gdb.org/db5.61browser/docs/topq/html), 1996.
Artzt, K., Barlow, D., Dove, W.F., Lindahl, J., Klein, J., Lyon, M.F., and Silver. L.M. Maps on mouse chromosome 17: First report. Mamm. Genome, 1:5–29, 1991.
Breslow, J.L. Insights into lipoprotein metabolism from studies in transgenic mice. Ann. Rev. Physiol., 56:797–810, 1994.
Breslow, J.L. Mouse models of atherosclerosis. Science, 272:685–688, 1996.
Bu, X., Warden, C.H., Xia, Y-R., DeMeester, C., Puppione, D.L., Teruya, S., Lokensgard, B., Daneshmand, S., Brown, J., Gray, R., Rotter, J.I., and Lusis, A.J. Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition: evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci. Hum. Genet., 93:639–648, 1994.
Collins, A., Lawrence, S., and Shields, D.C. Algorithms for a local database. Ann. Hum. Genet., 56:223-232. (URL:http://cedar.genetics.soton.ac.uk/public.html/gene.html, 1992.
Collins, F. Positional cloning moves from perditional to traditional. Nat. Genet., 9:347–350, 1995.
Copeman, J.B., Cucca, F., Hearne, H.M., Cornell, R.J., Reed, P.W., Ronningen, K.S., Undlien, D.F., Nistico, L., Buzzetti, R., Tosi, R., Pociot, F., Nerup, J., Cornelis, F., Barnett, A.H., Bain, S.C., and Todd, J.A. Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31-q33. Nat. Genet., 9:80–85, 1995.
Davies, J.L., Kawaguchi, Y., Bennett, S.T., Copeman, J.B., Cordell, H.J., Pritchard, L.F., Reed, P.W., Gough, S.C.L., Jenkins, S.C., Palmer, S.M., Balfour, K.M., Rowe, B.R., Farrall, M., Barnett, AH., Bain, S.C., and Todd J.A. A genome-wide search for human type 1 diabetes susceptibility genes. Nature, 371:130–136, 1994.
Dietrich, W.F., Lander, E.S., Smith, J.S., Moser, A.R., Gould, K.A., Luongo, C., Borenstein, N., and Dove, W. Genetic identification of Mom-1, major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell, 75:631–639, 1993.
Doolittle, M.H., LeBoeuf, R.C., Warden, C.H., Bee, L.M., and Lusis, A.J. A polymorphism affecting apolipoprotein A-II translational efficiency determines high density lipoprotein size and composition. J. Biol. Chem., 265:16380–16388, 1990.
Fisler, J.S., Warden, C.H., Pace, M.J., and Lusis, A.J. BSB: Anew mouse model of multigenic obesity. Obesity Res., 1:271–280, 1993.
Goldstein, J.L. and Brown, M.S. The low density lipoprotein receptor: A key for unlocking a multifactorial disease. In: Etiology of Human Disease at the DNA Level. Lindsten, J. and Petterson, U., eds. pp. 129–140, Raven Press, N.Y., 1991.
Goldstein, J.L., Hobbs, H.H., and Brown, M.S. Familial hypercholesterolemia. In: The Metabolic and Molecular Bases of Inherited Disease. Scriver, C.R., Beaudet, AL., Sly, W.S., and Valle, D., editors, pp. 1981–2030, McGraw-Hill, Inc., New York, 1995.
Hedrick, C.C. and Lusis, A.J. Apolipoprotein A-II: A protein in search of a function. Can. J. Cardiol., 19:453–459, 1994.
Hobbs, H.H., Leitersdorf, E., Leffert, C.C., Cryer, D.R., Brown, M.S., and Goldstein, J.L. Evidence for a dominant gene that suppresses hypercholesterolemia in a family with defective low density lipoprotein receptors. J. Clin. Invest, 84:656–664, 1989.
Hua, X., Wu, J., Goldstein, J.L., Brown, M.S., and Hobbs, H.H. Structure of human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17q11.2 and 22q13. Genomics, 25:667–673, 1995.
Keating, M.T. and Sanguinetti, M.C. Molecular genetic insights into cardiovascular disease. Science, 272:681–685, 1996.
Kleyn, P.W., Fan, W., Kovats, S.G., Lee, J.J., Pvledo, J.C., Wu, Y., Berkemeier, L.R., Misumi, D.J., Holmgren, L., Charlat, O., Woolf, E.A., Tayber, O., Brody, T., Shu, P., Hawkins, F., Kennedy, B., Baldini, L., Ebling, C., Alperin, G.D., Deeds I., Lakey, N.D., Colpepper, J., Chen, H., Glücksmann-Kuis, M.A., Carlson, G.A., Duyk, G.M., and Moore, K.J. Identification and characterization of the mouse obesity gene tubby: A member of a novel gene family. Cell, 85:281–290, 1996.
Kruglyak, L. and Lander, E.S. High resolution genetic mapping of complex traits. Am. J. Hum. Genet., 56:1212–1223, 1995.
Ivandic, B.T., Qiao, J-H., Machleder, D., Liao, F., Drake, T.A., and Lusis, A.J. A locus on chromosome 7 determines myocardial cell necrosis and calcification (dystrophic cardiac calcinosis) in mice. Proc. Nat. Acad. Sci. USA, 93:5483–5488, 1996.
Lander, E.S. and Schork, N.J. Genetic dissection of complex traits. Science, 265:2037–2048, 1994.
Lifton, R.P. Molecular genetics of human blood pressure variation. Science, 272:676–680, 1996.
Lusis, A.J. Genetic factors in atherosclerosis: the candidate gene approach. J. Lipid Res., 29:397–429, 1988.
Mehrabian, M., Demer, L.L., and Lusis, A.J. Differential accumulation of the intimai monocyte-macrophages relative to lipoproteins and lipofuscin correspond to hemodynamic forces on cardiac valves in mice. Arterioscl. Thromb., 11:947–957, 1991.
Mehrabian, M., Qiao, J.-H., Hyman, R., Ruddle, D., Laughton, C., and Lusis, A.J. Influence of the apoA-II gene locus on HDL levels and fatty streak development in mice. Arterioscl. Thromb., 13:1–10, 1993.
Noben-Trauth, K., Naggert, J.K., North, M.A., and Nishina, P.M. A candidate gene for the mouse mutation tubby. Nature, 380:534–538, 1996.
Paterniti, J.R., Brown, W.V., Ginsberg, H.N., and Artzt, K. Combined lipase deficiency (cld): A lethal mutation on chromosome 17 of the mouse. Science, 221:167–169, 1983.
Purcell-Huynh, D.A., Weinreb, A., Castellani, L.W., Mehrabian, M., Doolittle, M.H., and Lusis, A.J. Genetic factors in lipoprotein metabolism: Analysis of a genetic cross between mouse strains NZB/BINJ and SM/J using a complete linkage map approach. J. Clin. Invest., 96:1845–1858, 1995.
Qiao, J.-H., Welch, C.L., Xie, P.-Z., Fishbein, M.C., and Lusis, A.J. Involvement of the tyrosinase gene in deposition of cardiac lipofuscin in mice: Association with aortic fatty streak development. J. Clin. Invest., 92:2386–2393,1993.
Qiao, J-H., Xie, P-X., Fishbein, M.C., Kreuzer, J., Drake, T., Demer, L.L., and Lusis, A.J. Pathology of atheromatous lesions in inbred and genetically engineered mice: Genetic determination of arterial calcification. Arterioscl. Thromb., 14:1480–1497, 1994.
Reue, K. and Doolittle, M.H. Naturally occurring mutations in mice affecting lipid transport and metabolism. J. Lipid Res., 37:1387–1405, 1996.
Shih, D.M., Gu, L., Hama, S., Xia, Y-R., Navab, M., Fogelman, A.M., and Lusis, A.J. Genetic-dietary regulation of serum paraoxanase expression and its role in atherogenesis in a mouse model. J. Clin. Invest., 96:1630–1639, 1996.
Shih, D.M., Welch, C., and Lusis, A.J. New insights into atherosclerosis from studies with mouse models. Molec. Med. Today, 1:364–372, 1995.
Silver, L.M., Nadeau, J.H., and Goodfellow, P.N., eds. Mouse chromosome committee reports. Mamm. Genome, 5 (Suppl.).
Silver, L.M. Mouse Genetics: Concepts and Applications. Oxford University Press, New York.
Smithies, O. and Maeda, N. Gene targeting approaches to complex genetic diseases: Atherosclerosis and essential hypertension. Proc. Natl. Acad. Sci. USA, 92:5266–5272, 1995.
Wang, X., Sato, R., Brown, M.S., and Goldstein, J.L. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell, 77:53–62, 1994.
Warden, C.H., Daluiski, A., Bu, X., Purcell-Huynh, DA., DeMeester, C., Shieh, B.-H., Puppoine, D.L., Gray, R.M., Reaven, G.M., Chen, Y.-D. I., Rotter J.I., and Lusis, A.J. The apolipoprotein All gene determines plasma apolipoprotein AII levels and free fatty acid levels in both humans and mice. Proc. Nat. Acad. Sci. USA, 90:10886–10890, 1993a.
Warden, C.H., Fisler, J.S., Shoemaker, S.M., Wen, P-Z., Svenson, K.L., Pace, M.J., and Lusis, A.J. Identification of four chromosomal loci determining obesity in a multifactorial mouse model. J. Clin. Invest., 95:1545–1552, 1995.
Warden, C.H., Hedrick, C.C., Qiao, J.-H., Castellani, L.W., and Lusis, A.J. Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II. Science, 261:469–472, 1993b.
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Allayee, H. et al. (1998). Genetic Factors in Atherosclerosis. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 294. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0133-0_12
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DOI: https://doi.org/10.1007/978-1-4899-0133-0_12
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