Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia

P. Roma, R. E. Gregg, C. Bishop, R. Ronan, L. A. Zech, M. V. Meng, C. Glueck, C. Vergani, G. Guidici, H. B. Brewer

Research output: Contribution to journalArticle

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Abstract

Familial hypoalphalipoproteinemia (hypoalpha), characterized by a decreased high density lipoprotein level, is associated with an increased incidence of premature cardiovascular disease. Restriction fragment length polymorphism analysis of genomic DNA has detected a polymorphism for the PstI restriction endonuclease near the apoA-I gene, with either a 2.2 or a 3.3 kb fragment. The latter has been previously found to occur with significantly higher frequency in probands of families with familial hypoalpha. ApoA-I was isolated from three unrelated subjects with familial hypoalpha and the 3.3 kb PstI polymorphism of the apoA-I gene, and from normal control subjects. The apoA-I from the hypoalpha subjects was structurally normal as determined by amino acid analysis and by two-dimensional gel electrophoresis. When normal apoA-I and hypoalpha apoA-I were simultaneously injected into either normal controls or hypoalpha subjects, both forms of apoA-I were catabolized at the same rate in the same subject, indicating that the hypoalpha apoA-I is also metabolically normal. Analysis of the kinetics of metabolism of apoA-I in the hypoalpha subjects, compared to the normal controls, revealed that the reduced plasma levels of apoA-I were due to an increased apoA-I fractional catabolic rate, and that the synthetic rate was normal. Based on these results, we conclude that the apoA-I gene in these hypoalpha subjects is normal, and the PstI polymorphism near the apoA-I gene, which is associated with familial hypoalpha, is likely to be a marker for a mutant gene closely linked to, but not in, the apoA-I gene.

Original languageEnglish
Pages (from-to)1753-1760
Number of pages8
JournalJournal of Lipid Research
Volume31
Issue number10
Publication statusPublished - 1990

Fingerprint

Hypoalphalipoproteinemias
Apolipoprotein A-I
Polymorphism
Metabolism
Restriction Fragment Length Polymorphisms
Genes
Enzyme kinetics

Keywords

  • high density lipoproteins
  • residence time

ASJC Scopus subject areas

  • Endocrinology

Cite this

Roma, P., Gregg, R. E., Bishop, C., Ronan, R., Zech, L. A., Meng, M. V., ... Brewer, H. B. (1990). Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia. Journal of Lipid Research, 31(10), 1753-1760.

Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia. / Roma, P.; Gregg, R. E.; Bishop, C.; Ronan, R.; Zech, L. A.; Meng, M. V.; Glueck, C.; Vergani, C.; Guidici, G.; Brewer, H. B.

In: Journal of Lipid Research, Vol. 31, No. 10, 1990, p. 1753-1760.

Research output: Contribution to journalArticle

Roma, P, Gregg, RE, Bishop, C, Ronan, R, Zech, LA, Meng, MV, Glueck, C, Vergani, C, Guidici, G & Brewer, HB 1990, 'Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia', Journal of Lipid Research, vol. 31, no. 10, pp. 1753-1760.
Roma, P. ; Gregg, R. E. ; Bishop, C. ; Ronan, R. ; Zech, L. A. ; Meng, M. V. ; Glueck, C. ; Vergani, C. ; Guidici, G. ; Brewer, H. B. / Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia. In: Journal of Lipid Research. 1990 ; Vol. 31, No. 10. pp. 1753-1760.
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abstract = "Familial hypoalphalipoproteinemia (hypoalpha), characterized by a decreased high density lipoprotein level, is associated with an increased incidence of premature cardiovascular disease. Restriction fragment length polymorphism analysis of genomic DNA has detected a polymorphism for the PstI restriction endonuclease near the apoA-I gene, with either a 2.2 or a 3.3 kb fragment. The latter has been previously found to occur with significantly higher frequency in probands of families with familial hypoalpha. ApoA-I was isolated from three unrelated subjects with familial hypoalpha and the 3.3 kb PstI polymorphism of the apoA-I gene, and from normal control subjects. The apoA-I from the hypoalpha subjects was structurally normal as determined by amino acid analysis and by two-dimensional gel electrophoresis. When normal apoA-I and hypoalpha apoA-I were simultaneously injected into either normal controls or hypoalpha subjects, both forms of apoA-I were catabolized at the same rate in the same subject, indicating that the hypoalpha apoA-I is also metabolically normal. Analysis of the kinetics of metabolism of apoA-I in the hypoalpha subjects, compared to the normal controls, revealed that the reduced plasma levels of apoA-I were due to an increased apoA-I fractional catabolic rate, and that the synthetic rate was normal. Based on these results, we conclude that the apoA-I gene in these hypoalpha subjects is normal, and the PstI polymorphism near the apoA-I gene, which is associated with familial hypoalpha, is likely to be a marker for a mutant gene closely linked to, but not in, the apoA-I gene.",
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AU - Roma, P.

AU - Gregg, R. E.

AU - Bishop, C.

AU - Ronan, R.

AU - Zech, L. A.

AU - Meng, M. V.

AU - Glueck, C.

AU - Vergani, C.

AU - Guidici, G.

AU - Brewer, H. B.

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N2 - Familial hypoalphalipoproteinemia (hypoalpha), characterized by a decreased high density lipoprotein level, is associated with an increased incidence of premature cardiovascular disease. Restriction fragment length polymorphism analysis of genomic DNA has detected a polymorphism for the PstI restriction endonuclease near the apoA-I gene, with either a 2.2 or a 3.3 kb fragment. The latter has been previously found to occur with significantly higher frequency in probands of families with familial hypoalpha. ApoA-I was isolated from three unrelated subjects with familial hypoalpha and the 3.3 kb PstI polymorphism of the apoA-I gene, and from normal control subjects. The apoA-I from the hypoalpha subjects was structurally normal as determined by amino acid analysis and by two-dimensional gel electrophoresis. When normal apoA-I and hypoalpha apoA-I were simultaneously injected into either normal controls or hypoalpha subjects, both forms of apoA-I were catabolized at the same rate in the same subject, indicating that the hypoalpha apoA-I is also metabolically normal. Analysis of the kinetics of metabolism of apoA-I in the hypoalpha subjects, compared to the normal controls, revealed that the reduced plasma levels of apoA-I were due to an increased apoA-I fractional catabolic rate, and that the synthetic rate was normal. Based on these results, we conclude that the apoA-I gene in these hypoalpha subjects is normal, and the PstI polymorphism near the apoA-I gene, which is associated with familial hypoalpha, is likely to be a marker for a mutant gene closely linked to, but not in, the apoA-I gene.

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