Summary
High-density lipoprotein (HDL) cholesterol levels have an inverse relationship with the frequency of coronary and cerebrovascular disease. Most commonly HDL deficiency is environmentally modulated. Familial hypoalphalipoproteinemia (FHA) is a genetically determined HDL deficiency disease, in all likelihood transmitted as an autosomal dominant trait and associated with premature atherosclerosis. Apolipoprotein AI (apo AI) is the major apoprotein in the HDL particle, and defects in this protein have been suggested as the cause of FHA. We have identified a large family of Spanish descent with FHA and performed genetic linkage analysis using restriction fragment length polymorphisms in the Apo AI-CIII-AIV gene cluster to test this hypothesis. Results in this family formally exclude the apo AI-CIII-AIV gene cluster as the site for the mutation underlying FHA.
Similar content being viewed by others
References
Allain CC, Poon LS, Chan CS, Richmond W, Fu PC (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20:470–475
Avogaro P, Bittolo Bon G, Cazzolato G, Rorai E (1980) Relationship between apolipoproteins and chemical components of lipoproteins in survivors of myocardial infarction. Atherosclerosis 37:69–76
Bucolo G, David H (1973) Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 19:476–482
Carlson LA, Philipson B (1979) Fish-eye disease. A new familial condition with massive corneal opacities and dyslipoproteinaemia. Lancet II:921–923
Castelli WP, Doyle JT, Gordon T, Hames CG, Hjortland MC, Hulley SB, Kagan A, Zukel WJ (1977) HDL cholesterol and other lipids in coronary heart disease: the cooperative lipoprotein phenotyping study. Circulation 55:767–772
Daniels SR, Bates S, Lukin RR, Benton C, Third J, Glueck CJ (1982) Cerebrovascular arteriopathy (arteriosclerosis) and ischemie childhood stroke. Stroke 13:360–365
Friedewald WT, Levy RI, Frederickson DS (1972) Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of the preparative ultra-contrifuge. Clin Chem 18:499–502
Gjone E, Norum KR, Glomset JA (1978) Familial lecithin cholesterol acyltransferase deficiency. In: Stanbury JB, Wyngaarden JB, Fredrickson DS (eds) The metabolic basis of inherited disease, 4th edn. McGraw-Hill, New York, pp 589–603
Glueck CJ, Daniels SR, Bates S, Benton C, Tracy T, Third JLHC (1982) Pediatrie victims of unexplained stroke and their families: familial lipid and lipoprotein abnormalities. Pediatrics 69:308–316
Havel RJ, Eder HA, Bragdon JH (1955) The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 34:1345–1353
Hayden MR, Kirk H, Clark C, Frohlich J, Rabkin S, MacLeod R, Hewitt J (1987) DNA polymorphisms in and around the APO-AI-CIII genes and genetic hyperlipidemia. Am J Hum Genet 40:421–430
Herbert PN, Gotto AM, Frederickson DS (1978) Familial HDL deficiency. In: Stanbury JB, Wyngaarden JB, Fredrickson DS (eds) The metabolic basis of inherited disease, 4th edn. McGraw-Hill, New York, pp 544–588
Karathanasis SK (1985) Apolipoprotein multigene family: tandom organization of human apolipoprotein AI, CIII, and AIV genes. Proc Natl Acad Sci USA 82:6374–6379
Lathrop GM, Ott J, Lalouel JM, Julien C (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81:3443–3446
Maciejko JJ, Holmes DR, Kottke BA, Zinsmeister AR, Dinh DM, Mao SJT (1983) Apolipoprotein A-I as a marker of angiographically assessed coronary-artery disease. N Engl J Med 309:385–389
Malloy MJ, Kane JP (1982) Hypolipidemia. Med Clin North Am 66:469–484
Miller GJ, Miller NE (1975) Plasma-high-density-lipoprotein concentration and development of ischemic heart disease. Lancet 1:16–19
Norum RA, Lakier JB, Goldstein S, Angel A, Goldberg RB, Block W, Noffle DK, Dolphin P, Edelglass J, Bogorad DD, Alaupowic P (1982) Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease. N Engl J Med 306:1513–1519
Ordovas JM, Schaefer EJ, Deeb S, Ward RH, Glueck CJ, Vergani C, Wilson PWF, Karanthanasis SK (1986) Apolipoprotein AI gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia. N Engl J Med 314:671–677
Ott J (1974) Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet 26:588–597
Roma P, Gregg RE, Zech LA, Glueck C, Vergani C, Bishop C, Brever HB (1987) Abstract. Clin Res 35:320A
Sidoli A, Guidici G, Soria M, Vergani C (1986) Restriction-fragment-length polymorphisms in the A-I-C-III gene complex occurring in a family with hypoalphalipoproteinemia. Atherosclerosis 62:81–87
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 503–517
Third JLHC, Montag J, Flynn M, Freidel J, Laskarzewski P, Glueck CJ (1984) Primary and familial hypoalphalipoproteinemia. Metabolism 33:136–146
Vergani C, Bettale G (1981) Familial hypo-alpha-lipoproteinemia. Clin Chim Acta 114:45–52
Warnick GR, Aebers JJ (1978) A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 19:65–76
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kastelein, J.J.P., Haines, J.L. & Hayden, M.R. The gene causing familial hypoalphalipoproteinemia is not caused by a defect in the apo AI-CIII-AIV gene cluster in a Spanish family. Hum Genet 84, 396–400 (1990). https://doi.org/10.1007/BF00195807
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00195807