Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1991 Dec;49(6):1155–1166.

The gender-specific apolipoprotein E genotype influence on the distribution of lipids and apolipoproteins in the population of Rochester, MN. I. Pleiotropic effects on means and variances.

S L Reilly 1, R E Ferrell 1, B A Kottke 1, M I Kamboh 1, C F Sing 1
PMCID: PMC1686446  PMID: 1842218

Abstract

The influences of the apolipoprotein E (Apo E) polymorphism and of gender on the distributions of plasma levels of total cholesterol (Total-C), 1n triglycerides (1n Trig), HDL cholesterol (HDL-C), and apolipoproteins AI (Apo AI), AII (Apo AII), 1n E (1nApo E), B (Apo B), CII (Apo CII), and 1n CIII (1nApo CIII) were studied in 507 unrelated individuals representative of the adult population of Rochester, MN. Apo E genotypes influenced both phenotypic level and intragenotype phenotypic variability. The mean levels of six of the nine traits were influenced significantly by Apo E genotype. Intragenotype variability in eight of the nine traits was significantly different among Apo E genotypes. These effects were estimated separately in males and females. The contribution of allelic variation in the Apo E gene to the definition of the multivariate mena and variance of the lipid and apolipoprotein hyperspace was evaluated. These findings were used to demonstrate how heterogeneity of risk-factor-trait variance among genotype/gender-specific subgroups of the population at large may influence the evaluation of risk of coronary artery disease.

Full text

PDF
1156

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbott R. D., Garrison R. J., Wilson P. W., Epstein F. H., Castelli W. P., Feinleib M., LaRue C. Joint distribution of lipoprotein cholesterol classes. The Framingham study. Arteriosclerosis. 1983 May-Jun;3(3):260–272. doi: 10.1161/01.atv.3.3.260. [DOI] [PubMed] [Google Scholar]
  2. Anderson K. M., Wilson P. W., Garrison R. J., Castelli W. P. Longitudinal and secular trends in lipoprotein cholesterol measurements in a general population sample. The Framingham Offspring Study. Atherosclerosis. 1987 Nov;68(1-2):59–66. doi: 10.1016/0021-9150(87)90094-3. [DOI] [PubMed] [Google Scholar]
  3. Au Y. P., Bren N. D., Kottke B. A. A rapid apolipoprotein E radioimmunoassay using solid-phase staphylococcus protein. Use of pooled plasma as a secondary standard. Biochem Biophys Res Commun. 1986 Jul 16;138(1):455–462. doi: 10.1016/0006-291x(86)90302-5. [DOI] [PubMed] [Google Scholar]
  4. Au Y. P., Hallaway B. J., Kottke B. A. Use of a quality-control plasma sample to decrease interassay variation in radioimmunoassays of apolipoprotein A-I. Clin Chem. 1986 Jul;32(7):1394–1397. [PubMed] [Google Scholar]
  5. Barham D., Trinder P. An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst. 1972 Feb;97(151):142–145. doi: 10.1039/an9729700142. [DOI] [PubMed] [Google Scholar]
  6. Barr S. I., Kottke B. A., Chang J. Y., Mao S. J. Immunochemistry of human plasma apolipoprotein C-II as studied by radioimmunoassay. Biochim Biophys Acta. 1981 Feb 23;663(2):491–505. doi: 10.1016/0005-2760(81)90177-6. [DOI] [PubMed] [Google Scholar]
  7. Barr S. I., Kottke B. A., Mao S. J. Improved method for determination of triglycerides in plasma lipoproteins by an enzymic kit method. Clin Chem. 1981 Jun;27(6):1142–1144. [PubMed] [Google Scholar]
  8. Berg K. Variability gene effect on cholesterol at the Kidd blood group locus. Clin Genet. 1988 Feb;33(2):102–107. doi: 10.1111/j.1399-0004.1988.tb03419.x. [DOI] [PubMed] [Google Scholar]
  9. Bishop G. R., Mayo O., Beckman L. Possible influence of major gene heterozygosity on variation of quantitative traits. Hum Hered. 1988;38(4):216–227. doi: 10.1159/000153788. [DOI] [PubMed] [Google Scholar]
  10. Boerwinkle E., Utermann G. Simultaneous effects of the apolipoprotein E polymorphism on apolipoprotein E, apolipoprotein B, and cholesterol metabolism. Am J Hum Genet. 1988 Jan;42(1):104–112. [PMC free article] [PubMed] [Google Scholar]
  11. Boerwinkle E., Visvikis S., Welsh D., Steinmetz J., Hanash S. M., Sing C. F. The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals. Am J Med Genet. 1987 Jul;27(3):567–582. doi: 10.1002/ajmg.1320270310. [DOI] [PubMed] [Google Scholar]
  12. Ehnholm C., Lukka M., Kuusi T., Nikkilä E., Utermann G. Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations. J Lipid Res. 1986 Mar;27(3):227–235. [PubMed] [Google Scholar]
  13. Gordon T., Castelli W. P., Hjortland M. C., Kannel W. B., Dawber T. R. Diabetes, blood lipids, and the role of obesity in coronary heart disease risk for women. The Framingham study. Ann Intern Med. 1977 Oct;87(4):393–397. doi: 10.7326/0003-4819-87-4-393. [DOI] [PubMed] [Google Scholar]
  14. Gueguen R., Visvikis S., Steinmetz J., Siest G., Boerwinkle E. An analysis of genotype effects and their interactions by using the apolipoprotein E polymorphism and longitudinal data. Am J Hum Genet. 1989 Nov;45(5):793–802. [PMC free article] [PubMed] [Google Scholar]
  15. Hanis C. L., Hewett-Emmett D., Douglas T. C., Bertin T. K., Schull W. J. Effects of the apolipoprotein E polymorphism on levels of lipids, lipoproteins, and apolipoproteins among Mexican-Americans in Starr County, Texas. Arterioscler Thromb. 1991 Mar-Apr;11(2):362–370. doi: 10.1161/01.atv.11.2.362. [DOI] [PubMed] [Google Scholar]
  16. Havekes L. M., de Knijff P., Smit M., Frants R. R. The effect of apolipoprotein E allele substitutions on plasma lipid and apolipoprotein levels. Adv Exp Med Biol. 1988;243:87–93. doi: 10.1007/978-1-4613-0733-4_12. [DOI] [PubMed] [Google Scholar]
  17. Higgins M., Thom T. Trends in CHD in the United States. Int J Epidemiol. 1989;18(3 Suppl 1):S58–S66. [PubMed] [Google Scholar]
  18. Izzo C., Grillo F., Murador E. Improved method for determination of high-density-lipoprotein cholesterol I. Isolation of high-density lipoproteins by use of polyethylene glycol 6000. Clin Chem. 1981 Mar;27(3):371–374. [PubMed] [Google Scholar]
  19. Kamboh M. I., Ferrell R. E., Kottke B. Genetic studies of human apolipoproteins. V. A novel rapid procedure to screen apolipoprotein E polymorphism. J Lipid Res. 1988 Nov;29(11):1535–1543. [PubMed] [Google Scholar]
  20. Kaprio J., Ferrell R. E., Kottke B. A., Sing C. F. Smoking and reverse cholesterol transport: evidence for gene-environment interaction. Clin Genet. 1989 Oct;36(4):266–268. doi: 10.1111/j.1399-0004.1989.tb03201.x. [DOI] [PubMed] [Google Scholar]
  21. Kempthorne O. Logical, epistemological and statistical aspects of nature-nurture data interpretation. Biometrics. 1978 Mar;34(1):1–23. [PubMed] [Google Scholar]
  22. Kottke B. A., Zinsmeister A. R., Holmes D. R., Jr, Kneller R. W., Hallaway B. J., Mao S. J. Apolipoproteins and coronary artery disease. Mayo Clin Proc. 1986 May;61(5):313–320. doi: 10.1016/s0025-6196(12)61947-8. [DOI] [PubMed] [Google Scholar]
  23. Leibel R. L., Edens N. K., Fried S. K. Physiologic basis for the control of body fat distribution in humans. Annu Rev Nutr. 1989;9:417–443. doi: 10.1146/annurev.nu.09.070189.002221. [DOI] [PubMed] [Google Scholar]
  24. Lusis A. J. Genetic factors affecting blood lipoproteins: the candidate gene approach. J Lipid Res. 1988 Apr;29(4):397–429. [PubMed] [Google Scholar]
  25. Mahley R. W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988 Apr 29;240(4852):622–630. doi: 10.1126/science.3283935. [DOI] [PubMed] [Google Scholar]
  26. Menzel H. J., Kladetzky R. G., Assmann G. Apolipoprotein E polymorphism and coronary artery disease. Arteriosclerosis. 1983 Jul-Aug;3(4):310–315. doi: 10.1161/01.atv.3.4.310. [DOI] [PubMed] [Google Scholar]
  27. Moll P. P., Michels V. V., Weidman W. H., Kottke B. A. Genetic determination of plasma apolipoprotein AI in a population-based sample. Am J Hum Genet. 1989 Jan;44(1):124–139. [PMC free article] [PubMed] [Google Scholar]
  28. Nestruck A. C., Bouthillier D., Sing C. F., Davignon J. Apolipoprotein E polymorphism and plasma cholesterol response to probucol. Metabolism. 1987 Aug;36(8):743–747. doi: 10.1016/0026-0495(87)90110-7. [DOI] [PubMed] [Google Scholar]
  29. Ordovas J. M., Litwack-Klein L., Wilson P. W., Schaefer M. M., Schaefer E. J. Apolipoprotein E isoform phenotyping methodology and population frequency with identification of apoE1 and apoE5 isoforms. J Lipid Res. 1987 Apr;28(4):371–380. [PubMed] [Google Scholar]
  30. Pedersen J. C., Berg K. Interaction between low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) alleles contributes to normal variation in lipid level. Clin Genet. 1989 May;35(5):331–337. doi: 10.1111/j.1399-0004.1989.tb02953.x. [DOI] [PubMed] [Google Scholar]
  31. Reilly S. L., Kottke B. A., Sing C. F. The effects of generation and gender on the joint distributions of lipid and apolipoprotein phenotypes in the population at large. J Clin Epidemiol. 1990;43(9):921–940. doi: 10.1016/0895-4356(90)90076-2. [DOI] [PubMed] [Google Scholar]
  32. Rose G. Sick individuals and sick populations. Int J Epidemiol. 1985 Mar;14(1):32–38. doi: 10.1093/ije/14.1.32. [DOI] [PubMed] [Google Scholar]
  33. Sing C. F., Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet. 1985 Mar;37(2):268–285. [PMC free article] [PubMed] [Google Scholar]
  34. Sing C. F., Orr J. D. Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh, Michigan. III. Identification of genetic effects using 12 polymorphic genetic blood marker systems. Am J Hum Genet. 1976 Sep;28(5):453–464. [PMC free article] [PubMed] [Google Scholar]
  35. Thom T. J. International mortality from heart disease: rates and trends. Int J Epidemiol. 1989;18(3 Suppl 1):S20–S28. [PubMed] [Google Scholar]
  36. Truett J., Cornfield J., Kannel W. A multivariate analysis of the risk of coronary heart disease in Framingham. J Chronic Dis. 1967 Jul;20(7):511–524. doi: 10.1016/0021-9681(67)90082-3. [DOI] [PubMed] [Google Scholar]
  37. Van Valen L. Multivariate structural statistics in natural history. J Theor Biol. 1974 May;45(1):235–247. doi: 10.1016/0022-5193(74)90053-8. [DOI] [PubMed] [Google Scholar]
  38. Wilson P. W., Garrison R. J., Abbott R. D., Castelli W. P. Factors associated with lipoprotein cholesterol levels. The Framingham study. Arteriosclerosis. 1983 May-Jun;3(3):273–281. doi: 10.1161/01.atv.3.3.273. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES