Lipoprotein Metabolism

  • H. B. Brewer
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 109)


Plasma lipids are transported by lipoproteins composed of several classes of lipids (including cholesterol, triglycerides, and phospholipids) and proteins designated apolipoproteins. Our understanding of the role of lipoproteins and apolipoproteins in lipid transport has markedly increased over the last two decades. The roles of lipoprotein receptors, enzymes, and apolipoproteins in lipoprotein metabolism have been elucidated, and this new information provides a conceptual framework for the understanding of lipid transport in normal subjects and dyslipoproteinemic patients.


Cholesteryl Ester Cholesteryl Ester Transfer Protein Lipoprotein Metabolism Hepatic Lipase Lipoprotein Particle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Alaupovic P (1972) Conceptual development of the classification systems of plasma lipoproteins. Protides of the biological fluids. Proceedings of the 19th colloquium 9–19Google Scholar
  2. Armstrong VW, Cremer P, Eberle E, Manke A, Schulze F, Wieland H, Kreuzer H, Seidel D (1986) The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels. Atherosclerosis 62:249–257PubMedCrossRefGoogle Scholar
  3. Azrolan N, Gavish D, Breslow JL (1990) Lp(a) levels correlate inversely with apo(a) size and KIV copy number but not with apo(a) mRNA levels in a cynomolgus monkey model. Circulation 82:III-90Google Scholar
  4. Barbaras R, Puchois P, Fruchart JC, Ailhaud G (1987a) Cholesterol efflux from cultured adipose cells is mediated by LpAI particles but not by Lp AI:All particles. Biochem Biophys Res Commun 142:63–69CrossRefGoogle Scholar
  5. Barbaras R, Puchois P, Grimaldi P, Barkia A, Fruchart JC, Ailhaud G (1987b) Relationship in adipose cells between the presence of receptor sites for high density lipoproteins and the promotion of reverse cholesterol transport. Biochem Biophys Res Commun 149:545–554CrossRefGoogle Scholar
  6. Bekaert ED, Alaupovic P, Knight-Gibson CS, Laux MJ, Pelachyk JM, Norum RA (1991) Characterization of apoA- and apoB-containing lipoprotein particles in a variant of familial apoA-I deficiency with planar xanthoma: the metabolic significance of LP-A-II particles. JLR 32:1587–1599Google Scholar
  7. Berg K, Dahlen G, Frick MH (1974) Lp(a) lipoprotein and pre-betal-lipoprotein in patients with coronary heart disease. Clin Genet 6:230–235PubMedCrossRefGoogle Scholar
  8. Blackhart BD, Ludwig EM, Pierotti VR, Caiati L, Onasch MA, Wallis SC, Powell L, Pease R, Knott TJ, Chu ML, Scott MJ, McCarthy BJ, Levy-Wilson B (1986) Structure of the human apolipoprotein B gene. J Biol Chem 261:15364–15367PubMedGoogle Scholar
  9. Brewer HB Jr (1981) Current concepts of the molecular structure and metabolism of human apolipoproteins and lipoproteins. Klin Wochenschr 59:1023–1035PubMedCrossRefGoogle Scholar
  10. Breslow JL (1988) Apolipoprotein genetic variation and human disease. Physiol Rev 68:85–132PubMedGoogle Scholar
  11. Brewer HB Jr, Zech LA, Gregg RE, Schwartz D, Schaefer EJ (1983) Type III hyperlipoproteinemia: diagnosis, molecular defects, pathology, and treatment. Ann Intern Med 98:623–640PubMedGoogle Scholar
  12. Brewer HB Jr, Gregg Re, Hoeg JM, Fojo SS (1988) Apolipoproteins and lipoproteins in human plasma: an overview. Clin Chem 34:4–8Google Scholar
  13. Brewer HB Jr, Gregg RE, Hoeg JM (1989) Apolipoproteins, lipoproteins, and atherosclerosis. In: Braunwald E (ed) Heart disease: a textbook of cardiovascular medicine, 3rd edn. Saunders, New York, pp 121–144Google Scholar
  14. Chen SH, Habib G, Yang CY, Gu ZW, Lee BR, Weng SA, Silberman SR, Cai SJ, Deslypere JP, Rosseneu M, Gotto AM Jr, Li WH, Chan L (1987) Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon. Science 238:363–366PubMedCrossRefGoogle Scholar
  15. Cheung MC, Albers JJ (1984) Characterization of lipoprotein particles isolated by immunoaffinity chromatography. Particles containing A-I and A-II and particles containing A-I but no A-II. J Biol Chem 259:12201–12209PubMedGoogle Scholar
  16. Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8:1–21PubMedCrossRefGoogle Scholar
  17. Dawson PA, Hofman SL, Van der Westhuyzen DR, Sudhof TC, Brown MS, Goldstein JL (1988) Sterol-dependent repression of low density lipoprotein receptor promoter mediated by 16-base pair sequence adjacent to binding site for transcription factor Spl. J Biol Chem 263:3372–3379PubMedGoogle Scholar
  18. Deeb SS, Cheung MC, Peng R, Wolf AC, Stern R, Albers JJ, Knopp RH (1991) A mutation in the human apolipoprotein A-I gene. Dominant effect on the level and characteristics of plasma high density lipoproteins. J Biol Chem 266:13654–13660PubMedGoogle Scholar
  19. Eaton DL, Fless GM, Kohr WJ, McLean JW, Xu QT, Miller CG, Lawn RM, Scanu AM (1987) Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. Proc Natl Acad Sci USA 84:3224–3228PubMedCrossRefGoogle Scholar
  20. Edge SB, Hoeg JM, Triche T, Schneider PD, Brewer HB Jr (1986) Cultured human hepatocytes. Evidence for metabolism of low density lipoproteins by a pathway independent of the classical low density lipoprotein receptor. J Biol Chem 261:3800–3806PubMedGoogle Scholar
  21. Eisenberg S (1984) High density lipoprotein metabolism. J Lipid Res 25:1017–1058PubMedGoogle Scholar
  22. Fielding CJ, Shore VG, Fielding PE (1972) A protein cofactor of lecithin: cholesterol acyltransferase. Biochem Biophys Res Commun 46:1493–1498PubMedCrossRefGoogle Scholar
  23. Fless GM, Rolih CA, Scanu AM (1984) Heterogeneity of human plasma lipoprotein (a). Isolation and characterization of the lipoprotein subspecies and their apoproteins. J Biol Chem 259:11470–11478PubMedGoogle Scholar
  24. Gaubatz JW, Heideman C, Gotto AM Jr, Morrisett JD, Dahlen GH (1983) Human plasma lipoprotein [a]. Structural properties. J Biol Chem 258:4582–4589PubMedGoogle Scholar
  25. Glomset JA (1968) The plasma lecithin: cholesterol acyltransferase reaction. J Lipid Res 9:155–167PubMedGoogle Scholar
  26. Glomset JA, Janssen ET, Kennedy R, Dobbins J (1966) Role of plasma lecithin: cholesterol acyltransferase in the metabolism of high density lipoproteins. J Lipid Res 7:638–648PubMedGoogle Scholar
  27. Gofman JW, deLalla O, Glazier F et al. (1954) The serum lipid transport system in health, metabolic disorders, atherosclerosis, and coronary artery disease. Plasma 2:413–484Google Scholar
  28. Goldstein JL, Brown MS (1979) The LDL receptor locus and the genetics of familial hypercholesterolemia. Annu Rev Genet 13:259–289PubMedCrossRefGoogle Scholar
  29. Goldstein JL, Brown MS, Anderson RG, Russell DW, Schneider WJ (1985) Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. Annu Rev Cell Biol 1:1–39PubMedCrossRefGoogle Scholar
  30. Gordon DJ, Rifkind BM (1989) High-density lipoprotein — the clinical limplications of recent studies. N Engl J Med 321:1311–1316PubMedCrossRefGoogle Scholar
  31. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR (1977) High density lipoprotein as a protective factor against coronary heart disease. The Framingham study. Am J Med 63:707–714CrossRefGoogle Scholar
  32. Gregg RE, Brewer HB Jr (1988) The role of apolipoprotein E and lipoprotein receptors in modulating the in vivo metabolism of apolipoprotein B-containing lipoproteins in humans. Clin Chem 34:28–32Google Scholar
  33. Gregg RE, Zech LA, Schaefer EJ, Brewer HB Jr (1981) Type III hyperlipoproteinemia: defective metabolism of an abnormal apolipoprotein E. Science 211: 584–586Google Scholar
  34. Haberland ME, Fogelman AM (1987) The role of altered lipoproteins in the pathogenesis of atherosclerosis. Am Heart J 113:573–57PubMedCrossRefGoogle Scholar
  35. Havel RJ (1982) Familial dysbetalipoproteinemia. New aspects of pathogenesis and diagnosis. Med Clin North Am 66:441–454PubMedGoogle Scholar
  36. Havel RJ, Shore VG, Shore B, Bier DM (1970) Role of specific glycopeptides of human serum lipoproteins in the activation of lipoprotein lipase. Circ Res 27:595–600PubMedGoogle Scholar
  37. Herbert PN, Gotto AM Jr, Frederickson DS (1978) Familial lipoprotein deficiency (abetalipoproteinemia, hypobetalipoproteinemia, and Tangier disease). In: Stanberg JB, Wyngaarden JB, Frederickson DS (eds) Metabolic basis of inherited disease. McGraw-Hill, New York, pp 544–588Google Scholar
  38. Herz J, Hamann U, Rogne S, Myklebos O, Gausepohl H, Stanley KK (1988) Surface location and high affinity for calcium of a 500 kDa liver membrane protein closely related to the LDL receptor suggest a physiological role as a lipoprotein receptor. EMBO J 7:4119–4127PubMedGoogle Scholar
  39. Higuchi K, Hospattankar AV, Law SW, Meglin N, Cortright J, Brewer HB Jr (1988) Human apolipoprotein B (apoB) mRNA: identification of two distinct apoB mRNAs, an mRNA with the apoB-100 sequence and an apoB mRNA containing a premature in-frame translational stop codon, in both liver and intestine. Proc Natl Acad Sci USA 85:1772–1776PubMedCrossRefGoogle Scholar
  40. Hoeg JM, Edge SB, Demosky SJ Jr, Starzl TE, Triche T, Gregg RE, Brewer HB Jr (1986) Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects. Biochim Biophys Acta 876:646–657PubMedGoogle Scholar
  41. Hospattankar AV, Fairwell T, Ronan R, Brewer HB Jr (1984) Amino acid sequence of human plasma apolipoprotein C-II from normal and hyperlipoproteinemic subjects. J Biol Chem 259:318–322PubMedGoogle Scholar
  42. Hospattankar AV, Higuchi K, Law SW, Meglin N, Brewer HB Jr (1987) Identification of a novel in-frame translational stop codon in human intestine apoB mRNA. Biochem Biophys Res Commun 148:279–285PubMedCrossRefGoogle Scholar
  43. Jackson RL, Baker HN, Gilliam EB, Gotto AM Jr (1977) Primary structure of very low density apolipoprotein C-II of human plasma. Proc. Natl Acad Sci USA 74:1942–1945CrossRefGoogle Scholar
  44. Jahn CE, Osborne JC Jr, Schaefer EJ, Brewer HB Jr (1983) Activation of the enzymic activity of hepatic lipase by apolipoprotein A-II. Characterization of a major component of high density lipoprotein as the activating plasma component in vitro. Eur J Biochem 131:25–29PubMedCrossRefGoogle Scholar
  45. Kane JP (1983) Apolipoprotein B: structural and metabolic heterogeneity. Annu Rev Physiol 45:637–650PubMedCrossRefGoogle Scholar
  46. Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M (1990) Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature 343:531–535PubMedCrossRefGoogle Scholar
  47. Koschinsky ML, Beisiegel U, Henne-Bruns D, Eaton DL, Lawn RM (1990) Apolipoprotein(a) size heterogeneity is related to variable number of repeat sequences in its mRNA. Biochemistry 29:640–644PubMedCrossRefGoogle Scholar
  48. Kostner G, Alaupovic P (1972) Studies of the composition and structure of plasma lipoproteins. Separation and quantification of the lipoprotein families occurring in the high density lipoproteins of human plasma. Biochemistry 11:3419–3428PubMedCrossRefGoogle Scholar
  49. Kostner GM, Avagaro P, Zazzolato G, Marth E, Bittolo-Bon G, Quinci GB (1981) Lipoprotein Lp(a) and the risk for myocardial infarction. Arteriosclerosis 38:51–61CrossRefGoogle Scholar
  50. Lackner KJ, Monge JC, Gregg RE, Hoeg JM, Triche TJ, Law SW, Brewer HB Jr (1986) Analysis of the apolipoprotein B gene and messenger ribonucleic acid in abetalipoproteinemia. J Clin Invest 78:1707–1712PubMedCrossRefGoogle Scholar
  51. LaRosa JC, Levy RI, Herbert P, Lux SE, Fredrickson DS (1970) A specific apoprotein activator for lipoprotein lipase. Biochem Biophys Res Commun 41:57–62CrossRefGoogle Scholar
  52. Lee RS, Hatch RT (1963) Sharper separation of lipoprotein species by paper electrophoresis in albumin containing buffer. J Lab Clin Med 61:518–528Google Scholar
  53. Leppert M, Breslow JL, Wu L, Hasstedt S, O’Connell P, Lathrop M, Williams RR, White R, Lalouel JM (1988) Inference of a molecular defect of apolipoprotein B in hypobetalipoproteinemia by linkage analysis in a large kindred. J Clin Invest 82:847–851PubMedCrossRefGoogle Scholar
  54. Li WH, Tanimura M, Luo CC, Datta S, Chan L (1988) The apolipoprotein multigene family: biosynthesis, structure, structure—function relationships, and evolution. J Lipid Res 29:245–271PubMedGoogle Scholar
  55. Loscalzo J (1990) Lipoprotein(a). A unique risk factor for atherothrombotic disease. Arteriosclerosis 10:672–679PubMedCrossRefGoogle Scholar
  56. Mahley RW (1979) Dietary, fat, cholesterol, and accelerated atherosclerosis. Atherosclerosis Rev 5:1–34Google Scholar
  57. Mahley RW, Hui DY, Innerarity TL, Weisgraber KH (1981) Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man. Apo-B,E and apo-E receptors. J Clin Invest 68:1197–1206Google Scholar
  58. Mahley RW, Innerarity TL, Rall SC Jr, Weisgraber KH (1984) Plasma lipoproteins: apolipoprotein structure and function. J Lipid Res 25:1277–1294PubMedGoogle Scholar
  59. McKnight GL, Reasoner J, Gilbert T, Sundquist KO, Hokland B, McKernan PA, Champagne J, Johnson CJ, Bailey MC, Holly R, O’Hara PJ, Oram JF (1992) Cloning and expression of a cellular high density lipoprotein-binding protein that is up-regulated by cholesterol loading of cells. J Biol Chem 267:12131–12141PubMedGoogle Scholar
  60. McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM (1987) cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 330:132–137PubMedCrossRefGoogle Scholar
  61. Mendez AJ, Oram JF, Bierman EL (1991) Protein kinase C as a mediator of high density lipoprotein receptor-dependent efflux of intracellular cholesterol. J Biol Chem 266:10104–10111PubMedGoogle Scholar
  62. Miles LA, Plow EF (1990) Lp(a): an interloper in the fibrinolytic system. Thromb Haemost 63:331–335PubMedGoogle Scholar
  63. Miller GJ, Miller NE (1975) Plasma-high-density-lipoprotein concentration and development of ischaemic heart disease. Lancet 1:16–19PubMedCrossRefGoogle Scholar
  64. Miller NE, Thelle DS, Forde OH, Mjos OD (1977) The Tromso heart-study: high-density lipoproteins and coronary heart-disease: a prospective case-control study. Lancet 1:965–968PubMedCrossRefGoogle Scholar
  65. Mowri H-O, Patsch W, Smith LC, Gotto AM Jr, Patsch JR (1990) Different reactivities of HDL2 subfractions with hepatic lipase. Circulation 82:558Google Scholar
  66. Nestruck AC, Niedmann PD, Wieland H, Seidel D (1983) Chromatofocusing of human high density lipoproteins and isolation of lipoproteins A and A-I. Biochim Biophys Acta 753:65–73PubMedGoogle Scholar
  67. Norum RA, Lakier JB, Goldstein S, Angel A, Goldberg RB, Block WD, Noffze DK, Dolphin PJ, Edelglass J, Bogorad DD, Alaupovic P (1982) Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease. N Engl J Med 306:1513–1519PubMedCrossRefGoogle Scholar
  68. Oram JF, Brinton EA, Bierman EL (1983) Regulation of high density lipoprotein receptor activity in cultured human skin fibroblasts and human arterial smooth muscle cells. J Clin Invest 72:1611–1621PubMedCrossRefGoogle Scholar
  69. Osborne JC Jr, Brewer FIB Jr (1977) The plasma lipoproteins. Adv Protein Chem 31:253–337PubMedCrossRefGoogle Scholar
  70. Powell LM, Wallis SC, Pease RJ, Edwards YH, Knott TJ, Scott J (1987) A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell 50:831–840PubMedCrossRefGoogle Scholar
  71. Puchois P, Kandoussi A, Fievet P, Fourrier JL, Bertrand M, Koren E, Fruchart JC (1987) Apolipoprotein A-I containing lipoproteins in coronary artery disease. Atherosclerosis 68:35–40PubMedCrossRefGoogle Scholar
  72. Rader DJ, Castro G, Zech LA, Fruchart JC, Brewer HB Jr (1991) in vivo metabolism of apolipoprotein A-I on high density lipoprotein particles LpA-I and LpAI, A-II. J Lipid Res 32:1849–1859PubMedGoogle Scholar
  73. Rall SC Jr, Weisgraber KH, Mahley RW (1982) Human apolipoprotein E. The complete amino acid sequence. J Biol Chem 257:4171–4178PubMedGoogle Scholar
  74. Ross RS, Gregg RE, Law SW, Monge JC, Grant SM, Higuchi K, Triche TJ, Jefferson J, Brewer HB Jr (1988) Homozygous hypobetalipoproteinemia: a disease distinct from abetalipoproteinemia at the molecular level. J Clin Invest 81:590–595PubMedCrossRefGoogle Scholar
  75. Russell DW, Esser V, Hobbs HH (1989) Molecular basis of familial hypercholesterolemia. Arteriosclerosis [Suppl I] 9:1–8Google Scholar
  76. Scanu AM, Landsberger FR (1980) Lipoprotein structure. Ann NY Acad Sci 384:1–436Google Scholar
  77. Schaefer EJ, Ordovas JM, Law SW, Ghiselli G, Kashyap ML, Srivastava LS, Heaton WII, Albers JJ, Connor WE, Lindgren FT, Lemeshev Y, Segrest JP, Brewer HB Jr (1985) Familial apolipoprotein A-I and C-III deficiency, variant II. J Lipid Res 26:1089–1101PubMedGoogle Scholar
  78. Schmitz G, Lackner K (1989) High density lipoprotein deficiency with xanthomas: a defect in apoA-I synthesis. In: Crepaldi G, Baggio G (eds) Atherosclerosis VIII. Tekno, Rome, pp 399–403Google Scholar
  79. Schmitz G, Niemann R, Brennhausen B, Krause R, Assmann G (1985) Regulation of high density lipoprotein receptors in cultured macrophages: role of acyl-CoA: cholesterol acyltransferase. EMBO J 4:2773–2779PubMedGoogle Scholar
  80. Schultz JR, Verstuyft JG, Gong EL, Nichols AV, Rubin EM (1992) ApoAI and apoAl + apoAII trangenic mice: a comparison of atherosclerotic susceptibility. Circulation 86:1–472Google Scholar
  81. Steinberg D (1983) Lipoproteins and atherosclerosis. A look back and a look ahead. Arteriosclerosis 3:283–301PubMedCrossRefGoogle Scholar
  82. Steinberg D (1991) Antioxidants and atherosclerosis: a current assessment. Circulation 84:1420–1425PubMedGoogle Scholar
  83. Strickland DK, Ashcom JD, Williams S, Burgess WH, Migliorini M, Argraves WS (1990) Sequence identity between alpha2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor. J Biol Chem 265:17401–17404PubMedGoogle Scholar
  84. Sudhof TC, Goldstein JL, Brown MS, Russell DW (1985). The LDL receptor gene: a mosaic of exons shared with different proteins. Science 228:815PubMedCrossRefGoogle Scholar
  85. Suzuki N, Fidge N, Nestel P, Yin J (1983) Interaction of serum lipoproteins with the intestine. Evidence for specific high density lipoprotein-binding sites on isolated rat intestinal mucosal cells. J Lipid Res 24:253–264PubMedGoogle Scholar
  86. Tall AR (1986) Plasma lipid transfer proteins. J Lipid Res 27:361–367PubMedGoogle Scholar
  87. Theret N, Delbart C, Aguie G, Fruchart JC, Vassaux G, Ailhaud G (1990) Cholesterol efflux from adipose cells is coupled to diacylglycerol production and protein kinase C activation. Biochem Biophys Res Commun 173:1361–1368PubMedCrossRefGoogle Scholar
  88. Utermann G (1989) The mysteries of lipoprotein(a). Science 246:904–910PubMedCrossRefGoogle Scholar
  89. Utermann G, Weber W (1983) Protein composition of Lp(a) lipoprotein from human plasma. FEBS Lett 154:357–361PubMedCrossRefGoogle Scholar
  90. Utermann G, Vogelberg KH, Steinmetz A, Schoenborn W, Pruin N, Jaeschke M, Hees M, Canzler H (1979) Polymorphism of apolipoprotein E: II. Genetics of hyperlipoproteinemia type III. Clin Genet 15:37–62PubMedCrossRefGoogle Scholar
  91. Utermann G, Menzel HJ, Kraft HG, Duba HC, Kemmler HG, Seitz C (1987) Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. J Clin Invest 80:458–465PubMedCrossRefGoogle Scholar
  92. Van der Westhuyzen DR, Fourie AM, Coetzee GA, Gevers W (1990) The LDL receptor. Curr Opin Lipidol 1:128–135CrossRefGoogle Scholar
  93. Van Lenten BJ, Fogelman AM (1990) Processing of lipoproteins in human monocyte-macrophages. J Lipid Res 31:1455–1466PubMedGoogle Scholar
  94. Vega GL, Denke MA, Grundy SM (1991) Metabolic basis of primary hypercholesterolemia. Circulation 84:118–128PubMedGoogle Scholar
  95. Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M, Schmitz J, Gay G, Rader DJ, Gregg RE (1992) Absence of microsomal tri-glyceride transfer protein in individuals with abetalipoproteinemia. Science 258: 999–1001PubMedCrossRefGoogle Scholar
  96. Yamamoto T, Davis CG, Brown MS, Schneider WJ, Casey ML, Goldstein JL, Russell DW (1984) The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell 39:27–38PubMedCrossRefGoogle Scholar
  97. Zannis VI, Just PW, Breslow JL (1981) Human apolipoprotein E isoprotein subclasses are genetically determined. Am J Hum Genet 33:11–24PubMedGoogle Scholar

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  • H. B. Brewer

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