Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-26T23:52:10.176Z Has data issue: false hasContentIssue false
  • English
  • Français

Risk Factor Variability and Coronary Heart Disease

Published online by Cambridge University Press:  01 August 2014

K. Berg
K. Berg*
Affiliation:
Institute of Medical Genetics, University of Oslo, Norway Department of Medical Genetics, Ullevàl Hospital, Oslo, Norway
*
Institute of Medical Genetics, University of Oslo, P.O. Box 1036 Blindern, 0315 Oslo 3, Norway

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Present attempts to identify genes contributing to coronary heart disease (CHD) risk focus on “candidate genes”. With respect to CHD this could be any gene whose protein product is directly or indirectly involved in atherogenesis, thrombogenesis or thrombolysis/fibrinolysis. Genes that exhibit associations with absolute risk factor levels may be referred to as “level genes” to distinguish them from “variability genes”, which are genes involved in establishing the framework within which environmental influences may cause risk factor variation. In a series of persons recruited from the Norwegian Twin Panel, confirmatory evidence for level gene effect with respect to apolipoprotein B (apoB) concentration was found with an XbaI polymorphism in DNA at the apoB locus corresponding to residue 2,488 in the mature protein. Evidence for variability gene effect with respect to apoB as well as body mass index emerged with DNA variants in the 3′ part of the apoB gene. Level gene effect with respect to apolipoprotein A-I (apoA-I) and high density lipoprotein (HDL) cholesterol as well as apparent variability gene effect with respect to total and LDL cholesterol were detected with a DNA polymorphism at the cholesteryl ester transfer protein (CETP) locus. The first example of interaction between normal genes in determining risk factor level was uncovered in analysis of the apolipoprotein E (apoE) polymorphism and a restriction fragment length polymorphism (RFLP) at the low density lipoprotein receptor (LDLR) locus. An LDLR gene identified by presence of a PvuII restriction site eliminated completely the well known effect of the apoE4 allele on cholesterol level. Finally, in families where high Lp(a) lipoprotein level (a well established risk factor for CHD) segregated as a Mendelian trait, very close linkage with an RFLP at the plasminogen locus was established and DNA variation at the LPA locus reflecting varying numbers of a structure homologous to the “kringle IV” region of plasminogen was uncovered.

Keywords

HyperlipidemiaBody mass indexLipoproteinsAtherosclerosisCoronary heart diseaseCandidate genesDNA polymorphisms
Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 39 , Issue 1 , January 1990 , pp. 15 - 24
Copyright
Copyright © The International Society for Twin Studies 1990

References

REFERENCES

1.Berg, K (1963): A new serum type system in man - The Lp System. Acta Path Microbiol Scand 59:369–382.CrossRefGoogle ScholarPubMed
2.Berg, K, Dahlén, G, Frick, MH (1974): Lp(a) lipoprotein and pre-β1-lipoprotein in patients with coronary heart disease. Clin Genet 6:230–235.CrossRefGoogle ScholarPubMed
3.Berg, K, Hames, C, Dahlén, G, Frick, MH, Krishan, I (1976): Genetic variation in serum low-density lipoproteins and lipid levels in man. Proc Natl Acad Sei USA 73:937–940.CrossRefGoogle ScholarPubMed
4.Berg, K (1981): Twin research in coronary heart disease. In Gedda, L, Parisi, P, Nance, WE (eds): Twin Research 3: Part C, Epidemiological and Clinical Studies. New York: AR Liss, pp 117–130.Google Scholar
5.Berg, K (1984): Twin studies of coronary heart disease and its risk factors. Acta Genet Med Gemellol 33:349–361.Google ScholarPubMed
6.Berg, K (1986): DNA polymorphism at the apolipoprotein B locus is associated with lipoprotein level. Clin Genet 30:515–520.CrossRefGoogle ScholarPubMed
7.Berg, K, Powell, LM, Wallis, SC, Pease, R, Knott, TJ, Scott, J (1986): Genetic linkage between the antigenic group (Ag) variation and the apolipoprotein B gene: Assignment of the Ag locus. Proc Natl Acad Sei USA 83:7367–7370.Google Scholar
8.Berg, K (1987): Genetic risk factors for atherosclerotic disease. In Vogel, F, Sperling, K (eds): Human Genetics. Proceedings of the 7th International Congress of Human Genetics, Berlin 1986. Berlin: Springer-Verlag, pp 326–335.CrossRefGoogle Scholar
9.Berg, K (1987): Genetics of coronary heart disease and its risk factors. In Bock, G, Collins, GM (eds): Molecular Approaches to Human Polygenic Disease. Ciba Symposium 130. Chichester: John Wiley & Sons, pp 14–33.Google Scholar
10.Berg, K (1987): Genetics of atherosclerosis. In Olsson, AG (ed): Atherosclerosis. Biology and Clinical Science. Edinburgh: Churchill-Livingstone, pp 323–337.Google Scholar
11.Berg, K (1989): Molecular genetics and nutrition. J Clin Nutr (in press).Google Scholar
12.Berg, K (1989): Genetics of atherogenic Lp(a) lipoprotein. Paper presented at the Sig. K. Thoresen Symposium “From Phenotype to Gene in Common Disorderds”, Oslo, 05 18-20, 1989. Copenhagen: Munksgaard (in press).Google Scholar
13.Berg, K (1989): Level genes and variability genes in the etiology of hyperlipidemia and atherosclerosis. Paper presented at the Sig. K. Thoresen Symposium “From Phenotype to Gene in Common Disorders”, Oslo, 05 18-20, 1989. Copenhagen, Munksgaard (in press).Google Scholar
14.Berg, K, Kondo, I, Drayna, D, Lawn, R (1989): “Variability gene” effect of cholesteryl ester transfer protein (CETP) genes. Clin Gent 35:437–445.CrossRefGoogle ScholarPubMed
15.Beynen, AC, Katan, MB (1985): Reproducibility of the variations between humans in the response of serum cholesterol to cessation of egg consumption. Atherosclerosis 57:19–31.CrossRefGoogle ScholarPubMed
16.Brown, MS, Goldstein, JL (1987): Teaching old dogmas new tricks. Nature 330:113–114.CrossRefGoogle ScholarPubMed
17.Drayna, DT, Hegele, RA, Hass, PE, Emi, M, Wu, LL, Eaton, DL, Lawn, RM, Williams, RR, White, RL, Lalouel, J-M (1988): Genetic linkage between lipoprotein(a) phenotype and a DNA polymorphism in the plasminogen gene. Genomics 3:230–236.Google Scholar
18.Katan, MB, Beynen, AC, De Vries, JHM, Nobels, A (1986): Existence of consistent hypo- and hyperresponders to dietary cholesterol in man. Amer J Epidemiol 123:221–234.CrossRefGoogle ScholarPubMed
19.Katan, MB, Beynen, AC (1987): Characteristics of human hypo- and hyperresponders to dietary cholesterol. Amer J Epidemiol 125:387–399.CrossRefGoogle ScholarPubMed
20.Kondo, I, Berg, K, Drayna, D, Lawn, R (1989): DNA polymorphism at the locus for human cholesteryl ester transfer protein (CETP) is associated with high density lipoprotein cholesterol and apolipoprotein levels. Clin Genet 35:49–56.CrossRefGoogle ScholarPubMed
21.Kondo, I, Berg, K (1990): Inherited quantitative DNA variation in the LPA (“apolipoprotein (a)”) gene. Clin Genet 37:132–140.Google Scholar
22.Law, A, Powell, LM, Brunt, H, Knott, TJ, Altman, DG, Rajput, J, Wallis, SC, Pease, RJ, Priestley, LM, Scott, J, Miller, GJ, Miller, NE (1986): Common DNA polymorphism within the coding sequence of the apolipoprotein B gene associated with altered lipid levels. Lancet i:1301–1303.CrossRefGoogle Scholar
23.Maartmann-Moe, K, Magnus, P, Golden, W, Berg, K (1981): Genetics of the low density lipoprotein receptor: III. Evidence for multiple normal alleles at the low density lipoprotein receptor locus. Cin Genet 20:113–129.CrossRefGoogle ScholarPubMed
24.Magnus, P, Berg, K, Børresen, A-L, Nance, WE (1981): Apparent influence of marker genotypes on variation in serum cholesterol in monozygotic twins. Clin Genet 19:67–70.CrossRefGoogle Scholar
25.McLean, JW, Tomlinson, JE, Kuang, W-J, Eaton, OL, Chen, EY, Fless, GM, Scanu, AM, Lawn, RM (1987): cDNA sequence of human apolipoprotein (a) is homologous to plasminogen. Nature 330:132–137.CrossRefGoogle ScholarPubMed
26.Pedersen, JC, Berg, K (1988): Normal DNA polymorphism at the low density lipoprotein receptor locus associated with serum cholesterol level. Clin Genet 34:306–312.CrossRefGoogle ScholarPubMed
27.Pedersen, JC, Berg, K (1989): Interaction between low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) alleles contributes to normal variation in lipid level. Clin Genet 35:331–337.CrossRefGoogle ScholarPubMed
28.Rajput-Wilhams, J, Wallis, SC, Yarnell, J, Bell, BI, Knott, TJ, Sweetnam, P, Cox, N, Miller, NE, Scott, J (1988): Variation of apolipoprotein-B gene is associated with obesity, high blood cholesterol levels, and increased risk of coronary heart disease. Lancet ii: 1442–1446.CrossRefGoogle Scholar
29.Rhoads, GG, Dahlen, G, Berg, K, Morton, NE, Dannenberg, AI (1986): Lp(a) lipoprotein as a risk factor for myocardial infarction. JAMA 256:2540–2544.CrossRefGoogle ScholarPubMed
30.Weitkamp, LR, Guttormsen, SA, Schultz, JS (1988): Linkage between the loci for the Lp(a) lipoprotein (LP) and plasminogen (PLG). Hum Genet 79:80–82.Google Scholar