Skip to main content Accessibility help
×
Home

Distribution of apolipoprotein E phenotypes in Friedreich's ataxia

  • D. Bouthillier (a1), A.C. Nestruck (a1), R. Milne (a1), C.F. Sing (a2), A. Barbeau (a1) and J. Davignon (a1)...

Abstract

Allelic polymorphism at the apolipoprotein E (apo E) gene locus (alleles ɛ2, ɛ3 and ɛ4) is responsible for the existence of 6 discrete electrophoretic phenotypes of plasma apo E. Since the presence of the ɛ2 allele in the genotype tends to be associated with higher triglyceride levels, a study was undertaken to determine if a higher frequency of this allele could account for the presence of higher plasma triglycerides in subsets of patients with Friedreich's Ataxia. The frequency of the apo E phenotypes was determined in 37 subjects with Friedreich's Ataxia and compared with that of 102 normolipidemic and 102 hyperlipidemic individuals. There was no increased prevalence of the E3/2 phenotype and the ɛ2 allele in the Friedreich's sample as is found in a hyperlipidemic sample. Furthermore, the ɛ2 subset did not have significantly higher plasma triglycerides than the non-ɛ2 subset and the hypothesis was rejected. On the other hand, there was a trend for a decreased frequency of the E4/3 phenotype in the Friedreich's sample relative to the hyperlipidemic group but the difference did not reach statistical significance. The apo E phenotype distribution was also measured in a smaller sample of Charlevoix-Saguenay disease; this led to the discovery of two siblings with the relatively rare E2/2 phenotype and unexpectedly low levels of plasma lipid and lipoprotein concentrations. Plasma apolipoprotein E concentrations in both diseases were within the normal range except for subjects bearing the E2/2 phenotype.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Distribution of apolipoprotein E phenotypes in Friedreich's ataxia
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Distribution of apolipoprotein E phenotypes in Friedreich's ataxia
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Distribution of apolipoprotein E phenotypes in Friedreich's ataxia
      Available formats
      ×

Copyright

Corresponding author

Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W IR7

References

Hide All
Allain, CC, Poon, LS, Chan, FCS, Richmond, W, Fu, PC (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20:470475.
Barbeau, A (1976) Friedreich’s Ataxia 1976. An overview. Can J Neurol Sci 3:389397.
Blache, D, Bouthillier, D, Barbeau, A. Davignon, J (1982) Plasma lipoprotein lipase and hepatic lipase activities in Friedreich’s Ataxia. Can J Neurol Sci 9:191194.
Bouchard, JP, Barbeau, A, Bouchard, R. Bouchard, RW (1978) Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Can J Neurol Sci 5:6169.
Bouthillier, D, Sing, CF, Davignon, J (1983) Apolipoprotein? phenotyping with a single gel method — application to the study of informative matings. J Lipid Res 24:10601069.
Breslow, JL, Zannis, VI, Sangiacomo, TB, Third, JLHC. Tracy, T, Glueck, CJ (1982) Studies of familial type III hyperlipoproteinemia using as a genetic marker the apo? phenotype E2/2. J Lipid Res 23:12241235.
Curry, MD, McConathy, WJ, Alaupovic, P, Ledford, JH, Popovic, M (1976) Determination of human apolipoprotein? by electroimmuno-assay. Biochim Biophys Acta 439:413425.
Davignon, J, Huang, YS, Wolf, JP, Barbeau, A (1979) Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich’s Ataxia. Demonstration of a low linoleic acid content most evident in the cholesteryl-ester fraction. Can J Neurol Sci 6:275276.
Davignon, J, Bouthillier, D, Dufour, R. Lussier-Cacan, S (1983) Xanthomes et athérosclérose en présence de lipides sanguins normaux. Ann Méd Interne 134:483491.
Davignon, J, Sing, CF, Lussier-Cacan, S, Bouthillier, D (1984) Xanthelasma, latent dyslipoproteinemia and atherosclerosis: contribution of apo E polymorphism. In: De Gennes, JL, Polonovski, J and Paoletti, R (eds), Latent dyslipoproteinemia and atherosclerosis. Raven Press, New York, pp 213223.
Eiberg, H, Mohr, J, Nielsen, LS (1981) Linkage relationship between the locus for C3 and 47 polymorphic systems: confirmation of C3-Le linkage. (Abstract). Sixth Int Cong Human Genet, Jerusalem, p 147.
Elshourbagy, N, McLean, J, Mahley, R, Taylor, J (1984) Apolipoprotein E mRNA is relatively abundant in the brain, as well as in the liver and other tissues of marmosets and rats. Proceedings of the American Society of Biological Chemists, St Louis, MO, June 3 to 7, 1984.
Fredrickson, DS, Goldstein, JL, Brown, MS (1978) The familial hyperlipoproteinemias. In: The metabolic basis of inherited disease. Stanbury, JB, Wyngaarden, JB and Fredrickson, DS (eds). McGraw-Hill, New York, pp 604655.
Ghiselli, G, Gregg, RE, Zech, LA, Schaefer, EJ, Brewer, HB Jr (1982a) Phenotype study of apolipoprotein E isoforms in hyperlipoproteinemic patients. Lancet 2:405407.
Ghiselli, G, Schaefer, EJ, Zech, LA, Gregg, LE, Brewer, HB Jr (1982b) Increased prevalence of apolipoprotein E4 in type V hyperlipoproteinemia. J Clin Invest 70:474477.
Gregg, RE, Zech, LA, Schaefer, EJ, Brewer, HB Jr (1981) Type III hyperlipoproteinemia: defective metabolism of an abnormal lipoprotein E. Science 211:584585.
Gregg, RE, Ghiselli, G, Brewer, HB Jr (1983) Apolipoprotein E: Bethesda: a new variant of apolipoprotein E associated with type III hyperlipoproteinemia. J Clin Endocrinol Metab 57:969974.
Huang, YS, Nestruck, AC, Barbeau, A, Bouchard, JP, Davignon, J (1978) Plasma lipids and lipoproteins in Friedreich’s Ataxia and familial spastic ataxia — evidence for an abnormal composition of high density lipoproteins. Can J Neurol Sci 5:149156.
Huang, YS, Marcel, YL, Vezina, C, Barbeau, A, Davignon, J (1980) Lecithin-cholesterol acyltransferase activity and fatty acid composition of erythrocyte phospholipids in Friedreich’s Ataxia. Can J Neurol Sci 7:429434.
Mahley, RW, Innerarity, TL (1983) Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta 737:197222.
Manual of Laboratory Operations, Lipid Research Clinics Program (1974). USDept of HEW, Publication no: (NIH) 75–628, pp 181.
McLean, JW, Elshourbagy, NA, Chang, DJ, Mahley, RW, Taylor, JM (1983) Heterozygosity within the E3 genotype of human apolipoprotein ? as determined by nucleotide sequence analysis. Arteriosclerosis 3:514a.
Menzel, HJ, Kladetsky, RG, Assmann, G (1983) Apolipoprotein E polymorphism and coronary artery disease. Arteriosclerosis 3:310322.
Milne, RW, Douste-Blazy, Ph, Marcel, YL, Retegui, L (1981 (Characterization of monoclonal antibodies against human apolipoprotein E. J Clin Invest 68:111117.
Olaisen, B, Teisberg, P, Gedde-Dahl, T Jr (1982) The locus for apolipoprotein E (apo E) is linked to the complement component C3 (C3) locus on chromosome 19 in man. Hum Genet 62:233236.
Pourcher, E, Barbeau, A (1980) Field testing of an ataxia scoring and staging system. Can J Neurol Sci 7:339344.
Rall, SC Jr, Weisgraber, KH, Innerarity, TL, Mahley, RW (1983) Identical structural and receptor binding defects in apolipoprotein E2 in hypo-, normo- and hypercholesterolemic dysbetalipoproteinemia. J Clin Invest 71:10231031.
Rall, SC Jr, Weisgraber, KH, Innerarity, TL, Mahley, RW (1984) Structure and function of apolipoprotein E: existence of multiple E2 alleles in type III hyperlipoproteinemia. In: Latent dyslipoproteinemias and atherosclerosis. de Gennes, JL, Polonovski, J and Paoletti, R (eds). Raven Press, New York, pp 157163.
Roheim, PS, Carey, M, Forte, T, Vega, GL (1979) Apolipoproteins in human cerebrospinal fluid. Proc Natl Acad Sci USA 76:46464649.
Sampson, EJ, Demers, LM, Krieg, AF (1975) Faster enzymatic procedure for serum triglycerides. Clin Chem 21:19831985.
Schneider, WJ, Kovanen, PT, Brown, MS, Goldstein, JL, Utermann, G, Weber, W, Havel, RJ, Kotite, L, Kane, JP, Innerarity, TL, Mahley, RW (1981) Familial dysbetalipoproteinemia. Abnormal binding of mutant apolipoprotein E to low density lipoprotein receptors of human fibroblasts and membranes from liver and adrenals of rats, rabbits and cows. J Clin Invest 68:10751085.
Utermann, G, Pruin, N, Steinmetz, A (1979) Polymorphism of apolipoprotein E — III Effect of a single polymorphic gene locus on plasma lipid levels in man. Clin Genet 15:6372.
Utermann, G, Steinmetz, A, Weber, W (1982) Genetic control of human apolipoprotein E polymorphism: comparison of one- and two-dimensional techniques of isoprotein analysis. Hum Genet 60:344351.
Warnick, GR, Mayfield, C, Albers, JJ, Hazzard, WR (1979) Gel isoelectric focusing method for specific diagnosis of familial hyperlipoproteinemia type III. Clin Chem 25:279284.
Weisgraber, KH, Rall, SC, Mahley, RW (1981) Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo E isoform. J Biol Chem 256:90779083.
Zannis, VI, Breslow, JL (1981) Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and post-translational modification. Biochemistry 20: 10331041.

Distribution of apolipoprotein E phenotypes in Friedreich's ataxia

  • D. Bouthillier (a1), A.C. Nestruck (a1), R. Milne (a1), C.F. Sing (a2), A. Barbeau (a1) and J. Davignon (a1)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed