Skip to main content
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1988 Sep;43(3):311–321.

Sources of interindividual variation in the quantitative levels of apolipoprotein B in pedigrees ascertained through a lipid clinic.

G Pairitz 1, J Davignon 1, H Mailloux 1, C F Sing 1
PMCID: PMC1715383  PMID: 3414686

Abstract

The quantitative level of apolipoprotein (apo) B associated with low-density lipoprotein (LDL) varies among individuals within the population. This variation in level of the LDL receptor ligand appears to have predictive value, and may have an etiologic role, in coronary artery disease. Complex segregation analysis was used to compare eight different models of transmission. This study confirms the existence of allelic variations at a single genetic locus with large effects on the interindividual variation in the level of the serum apo B associated with LDL. This is the first study to consider the possible effects of inherited polymorphic variation in the apo E molecule when analyzing the components of variation in apo B associated with LDL. Our analyses suggest that the common alleles coding for the apo E polymorphism act independently of the unmeasured single-gene locus characterized by this study.

Full text

PDF
317

Selected References

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

  1. Allain C. C., Poon L. S., Chan C. S., Richmond W., Fu P. C. Enzymatic determination of total serum cholesterol. Clin Chem. 1974 Apr;20(4):470–475. [PubMed] [Google Scholar]
  2. Amos C. I., Elston R. C., Srinivasan S. R., Wilson A. F., Cresanta J. L., Ward L. J., Berenson G. S. Linkage and segregation analyses of apolipoproteins A1 and B, and lipoprotein cholesterol levels in a large pedigree with excess coronary heart disease: the Bogalusa Heart Study. Genet Epidemiol. 1987;4(2):115–128. doi: 10.1002/gepi.1370040206. [DOI] [PubMed] [Google Scholar]
  3. Avogaro P., Bon G. B., Cazzolato G., Quinci G. B. Are apolipoproteins better discriminators than lipids for atherosclerosis? Lancet. 1979 Apr 28;1(8122):901–903. doi: 10.1016/s0140-6736(79)91375-8. [DOI] [PubMed] [Google Scholar]
  4. Beaty T. H., Kwiterovich P. O., Jr, Khoury M. J., White S., Bachorik P. S., Smith H. H., Teng B., Sniderman A. Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia. Am J Hum Genet. 1986 Apr;38(4):492–504. [PMC free article] [PubMed] [Google Scholar]
  5. Beaumont J. L., Carlson L. A., Cooper G. R., Fejfar Z., Fredrickson D. S., Strasser T. Classification of hyperlipidaemias and hyperlipoproteinaemias. Bull World Health Organ. 1970;43(6):891–915. [PMC free article] [PubMed] [Google Scholar]
  6. Bouthillier D., Sing C. F., Davignon J. Apolipoprotein E phenotyping with a single gel method: application to the study of informative matings. J Lipid Res. 1983 Aug;24(8):1060–1069. [PubMed] [Google Scholar]
  7. Demenais F., Lathrop M., Lalouel J. M. Robustness and power of the unified model in the analysis of quantitative measurements. Am J Hum Genet. 1986 Feb;38(2):228–234. [PMC free article] [PubMed] [Google Scholar]
  8. Elston R. C., Stewart J. A general model for the genetic analysis of pedigree data. Hum Hered. 1971;21(6):523–542. doi: 10.1159/000152448. [DOI] [PubMed] [Google Scholar]
  9. Hasstedt S. J. A mixed-model likelihood approximation on large pedigrees. Comput Biomed Res. 1982 Jun;15(3):295–307. doi: 10.1016/0010-4809(82)90064-7. [DOI] [PubMed] [Google Scholar]
  10. Hasstedt S. J., Wu L., Williams R. R. Major locus inheritance of apolipoprotein B in Utah pedigrees. Genet Epidemiol. 1987;4(2):67–76. doi: 10.1002/gepi.1370040202. [DOI] [PubMed] [Google Scholar]
  11. Heiss G., Tamir I., Davis C. E., Tyroler H. A., Rifkand B. M., Schonfeld G., Jacobs D., Frantz I. D., Jr Lipoprotein-cholesterol distributions in selected North American populations: the lipid research clinics program prevalence study. Circulation. 1980 Feb;61(2):302–315. doi: 10.1161/01.cir.61.2.302. [DOI] [PubMed] [Google Scholar]
  12. MacLean C. J., Morton N. E., Lew R. Analysis of family resemblance. IV. Operational characteristics of segregation analysis. Am J Hum Genet. 1975 May;27(3):365–384. [PMC free article] [PubMed] [Google Scholar]
  13. Maclean C. J., Morton N. E., Elston R. C., Yee S. Skewness in commingled distributions. Biometrics. 1976 Sep;32(3):695–699. [PubMed] [Google Scholar]
  14. Reardon M. F., Poapst M. E., Uffelman K. D., Steiner G. Improved method for quantitation of B apoprotein in plasma lipoproteins by electroimmunoassay. Clin Chem. 1981 Jun;27(6):892–895. [PubMed] [Google Scholar]
  15. Riesen W. F., Mordasini R., Salzmann C., Theler A., Gurtner H. P. Apoproteins and lipids as discriminators of severity of coronary heart disease. Atherosclerosis. 1980 Sep;37(1):157–162. doi: 10.1016/0021-9150(80)90104-5. [DOI] [PubMed] [Google Scholar]
  16. Rosseneu M., Vinaimont N., Vercaemst R., Dekeersgieter W., Belpaire F. Standardization of immunoassays for the quantitation of plasma Apo B protein. Anal Biochem. 1981 Sep 1;116(1):204–210. doi: 10.1016/0003-2697(81)90345-6. [DOI] [PubMed] [Google Scholar]
  17. Sampson E. J., Demers L. M., Krieg A. F. Faster enzymatic procedure for serum triglycerides. Clin Chem. 1975 Dec;21(13):1983–1985. [PubMed] [Google Scholar]
  18. Schmidt S. B., Wasserman A. G., Muesing R. A., Schlesselman S. E., Larosa J. C., Ross A. M. Lipoprotein and apolipoprotein levels in angiographically defined coronary atherosclerosis. Am J Cardiol. 1985 Jun 1;55(13 Pt 1):1459–1462. doi: 10.1016/0002-9149(85)90953-1. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Sniderman A. D., Wolfson C., Teng B., Franklin F. A., Bachorik P. S., Kwiterovich P. O., Jr Association of hyperapobetalipoproteinemia with endogenous hypertriglyceridemia and atherosclerosis. Ann Intern Med. 1982 Dec;97(6):833–839. doi: 10.7326/0003-4819-97-6-833. [DOI] [PubMed] [Google Scholar]
  21. Sniderman A., Shapiro S., Marpole D., Skinner B., Teng B., Kwiterovich P. O., Jr Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc Natl Acad Sci U S A. 1980 Jan;77(1):604–608. doi: 10.1073/pnas.77.1.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sniderman A., Teng B., Genest J., Cianflone K., Wacholder S., Kwiterovich P., Jr Familial aggregation and early expression of hyperapobetalipoproteinemia. Am J Cardiol. 1985 Feb 1;55(4):291–295. doi: 10.1016/0002-9149(85)90363-7. [DOI] [PubMed] [Google Scholar]
  23. Teng B., Thompson G. R., Sniderman A. D., Forte T. M., Krauss R. M., Kwiterovich P. O., Jr Composition and distribution of low density lipoprotein fractions in hyperapobetalipoproteinemia, normolipidemia, and familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6662–6666. doi: 10.1073/pnas.80.21.6662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Whayne T. F., Alaupovic P., Curry M. D., Lee E. T., Anderson P. S., Schechter E. Plasma apolipoprotein B and VLDL-, LDL-, and HDL-cholesterol as risk factors in the development of coronary artery disease in male patients examined by angiography. Atherosclerosis. 1981 Jun;39(3):411–424. doi: 10.1016/0021-9150(81)90026-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES