Human Apolipoprotein Mutants 2: From Gene Structure to Phenotypic Expression

252 Pages·1989·10.253 MB·English

by  Sotirios K. Karathanasis (auth.), C. R. Sirtori, G. Franceschini, H. B. Brewer Jr., G. Assmann (eds.)

Human Apolipoprotein
Mutants 2
From Gene Structure to
Phenotypic Expression
NATO ASI Series
Advanced Science Institutes Series
A series presenting the results of activities sponsored by the NA TO Science Committee,
which aims at the dissemination of advanced scientific and technological knowledge,
with a view to strengthening links between scientific communities.
The series is published by an international board of publishers in conjunction with the
NATO Scientific Affairs Division
A Life Sciences Plenum Publishing Corporation
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C Mathematical Kluwer Academic Publishers
and Physical Sciences Dordrecht, Boston, and London
D Behavioral and Social Sciences
E Applied Sciences
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G Ecological Sciences Berlin, Heidelberg, New York, London,
H Cell Biology Paris, and Tokyo
Recent Volumes in this Series
Volume 166-Vascular Dynamics: PhYSiological Perspectives
edited by N. Westerhof and D. R. Gross
Volume 167-Human Apolipoprotein Mutants 2: From Gene Structure to
Phenotypic Expression
edited by C. R. Sirtori, G. Franceschini,
H. B. Brewer, Jr., and G. Assmann
Volume 168-Techniques and New Developments in Photosynthesis Research
edited by J. Barber and R. Malkin
Volume 169-Evolutionary Tinkering in Gene Expression
edited by Marianne Grunberg-Manago, Brian F. C. Clark,
and Hans G. Zachau
Volume 170-ras Oncogenes
edited by Demetrios Spandidos
Volume 171-Dietaryw3 and w6 Fatty Acids: Biological Effects
and Nutritional Essentiality
edited by-Claudio Galli and Artemis P. Simopoulos
Volume 172-RecentTrends in Regeneration Research
edited by V. Kiortsis, S. Koussoulakos, and H. Wallace
Series A: Life Sciences
Human Apolipoprotein
Mutants 2
From Gene Structure to
Phenotypic Expression
Edited by
c.
R. Sirtori and G. Franceschini
Institute of Pharmacological Sciences
University of Milan
Milan, Italy
H. B. Brewer, Jr.
National Heart, Lung, and Blood Institute
National Institutes of Health
Bethesda, Matyland
and
G. Assmann
University of MOnster
MOnster, Federal Republic of Germany
Plenum Press
New York and London
Published in cooperation with NATO Scientific Affairs Division
Proceedings of a NATO Advanced Research Workshop on
Human Apolipoprotein Mutants:
From Gene Structure to Phenotypic Expression,
held March 27-30,1988,
in Limone sui Garda, Italy
Library of Congress Cataloging in Publication Data
NATO Advanced Research Workshop on Human Apolipoprotein Mutants: from
Gene Structure to Phenotypic Expression (1988: Limone sui Garda, Italy)
Human apolipoprotein mutants 2.
(NATO ASI series. Series A, Life sciences; v. 167)
"Proceedings of a NATO Advanced Research Workshop on Human Apolipopro
tein Mutants: from Gene Structure to Phenotypic Expression, held March 27-30,
1988, in Limone sui Garda,ltaly"-T.p. verso.
"Published in cooperation with NATO Scientific Affairs Division."
Includes bibliographies and index.
1. Apolipoproteins-Congresses. 2. Gene expression-Congresses. 3. Human
chromosome abnormalities-Congresses. I. Sirtori, Cesare R. II. North Atlantic
Treaty Organization. Scientific Affairs Division. III. Title. IV. Series. [DNLM: 1.
ApolipoprQteins-genetics-congresses. 2. Gene Expression Regulation
congresses. 3. Mutation-congresses. OU 55 N28555h 1988]
OP99.3.A65N36 1988 573.2'292 89-8532
ISBN-13: 978-1-4615-9551-9 e-ISBN-13: 978-1-4615-9549-6
001: 10.10071978-1-4615-9549-6
© 1989 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1989
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
The pleasant community of Limone suI Garda provided outstanding
hospitality for a second NATO ARW dealing with apolipoprotein variants,
which are natures clues for the discovery of the physiological roles of
apolipoproteins in lipoprotein metabolism in normal subjects and
patients with specific dyslipoproteinemias.
Limone, the site of discovery of the first human apolipoprotein
mutant, apoA-I-Milano, provided a brilliant sunny spring venue for more
than 50 participants from both sides of the ocean.
The attendance at the colorful opening ceremony of the ARW was one
of the largest on record. Two members of the Italian government, the
Secretaries of Health and the Navy, gave the welcoming addresses. Six
television networks, two with national audiences, covered the
international workshop.
The Limone oracles provided a montage of insights gleamed from the
eyes of the clinican, the biochemist, and the molecular biologist. The
cumulative information on the molecular defects in lipoprotein
metabolism reviewed by this diverse group of investigators provided an
ever expanding horizon of new knowledge in this fast moving and some
times perplexing field. Clinical vignettes were presented on patients
from throughout the world including Canada (Connelly), Turkey (Schmitz),
and France (Infante) detailing the clinical sequelae of a defect in a
specific apolipoprotein. The clinical importance of Lp(a), a
lipoprotein relegated almost to obscurity for many years, has now taken
v
center stage. The increased risk of premature cardiovascular disease
associated with elevated plasma levels of Lp(a) will be a challenge to
the clinical investigator and physician since diet and the commonly used
drugs have little effects on plasma Lp(a) levels. Limone was also the
appropriate setting for the detailed description of the kinetic analysiS
of apoA-I-Milano metabolism, and a final explanation for the variable
plasma levels of this mutant apolipoprotein (Roma, Gregg, Sirtori,
Franceschini).
During the workshop, the evolution of the lipoprotein transport
system was delineated in detail (Chapman), and an update on the quest
for the apoE or remnant receptor was presented (Beisiegel).
From the molecular biologist view point, the stop codon became a
focal point of interest. The introduction of the stop codon at the DNA
level provided the mechanism for several defects in apolipoprotein
biosynthesis (Fojo, Baggio). The herculean struggle of the lipoprotein
chemist vs the apoB protein was finally resolved, and nature begrudging
finally lifted the curtain on the mechanism for the biosynthesis of
apoB-IOO and apoB-48 from the single apoB gene. Again the stop codon
provided the mechanism, this time being introduced at the RNA level by a
novel RNA editing mechanism. The elucidation of the covalent structure
of apoB and the discovering of the mechanism for the synthesis of
apoB-IOO and apoB-48 are striking example of the power of the tools
available to the molecular biologist.
The superstars of gene polymorphism (Karathanasis, Ordovas,
Baralle) presented thoughtful overviews on the use as well as the
limitations of RFLP's in the analysis of genetic defects in single
kindreds and large scale population studies. The limitation of RFLPs as
a screening test for individual at risk for the development of premature
cardiovascular disease has now become apparent.
vi
The venue. the hospitality of Limone. and the science at the second
ARW was exemplary. I also have to personally express our appreciation
to Cesare Sirtori and Guido Franceschini. our hosts. for the outstanding
organization of the meeting, and their untiring efforts to collect the
manuscripts for this book. We all look forward to the 3rd ARW on
apolipoprotein mutants.
H. Bryan Brewer. Jr., M.D.
Chief. Molecular Disease Branch
National Heart. Lung. and Blood Institute
National Institutes- of Health
Bethesda, Maryland. U.S.A.
CONTENTS
EVOLUTION AND CONTROL OF GENE EXPRESSION
Apolipoprotein Genes: Organization, Linkage
and Evolution ..•..••.•.•••••.••••.•••••.•...••.••.••••••..•...• " 1
S.K. Karathanasis
Apolipoprotein Variation: Effect on Plasma
Lipid Variabili ty •.•.•••.......••..•...•..•.••••..•...••...•...•. 9
G. Utermann
Expression of Human Apo AI, All and CII Genes
in Pro- and Eucaryotic Cells.................................... 17
W. Stoffel, E. Binczek, A. Haase and C. Holtfreter.
Cis-Acting Elements and Trans-Acting Factors
Involved in Cell Type Specific Expression of
the Human Apolipoprotein AI Gene ...•.••...••••...•••••.•.••••... 31
U. Seedorf, K.N. Sastry and S.K. Karathanasis
Human Apolipoprotein A-I: Studies on Gene Expression
and Site-Directed Mutagenesis in E.Coli •...•••...•.•......•.... 39
M. Soria, A. Isacchi, R. Lorenzetti, L. Monaco,
R. Palomba and P. Sarmientos
HIGH DENSITY LIPOPROTEINS AND APO AI-MILANO
Apolipoprotein AI-Milano: Mechanisms for the An tiatherogenic
Potential. • . . . • . . . • • • • • • • • . . . • • • . • • . • • • • . . • . • • • . • . . . • • • • . • • . • . .. 45
G. Franceschini, L. Calabresi, M. Baio,
A.V. Nichols and C.R. Sirtori
In Vivo Catabolism of Apolipoprotein A-I in Subjects
with Familial Hypoalphalipoproteinemia •....••••...••••..••..••.. 51
P. Roma, R.E. Gregg, M. Meng, C. Bishop, R. Ronan,
L.A. Zech, M.V. Meng, C. Glueck, C. Vergani, G.
Franceschini, C.R. Sirtori and H.B. Brewer Jr.
ix
Synthesis of Apolipoprotein A-I in the Skeletal Muscle
of the Developing Chick........................................ 59
S. Calandra and P. Tarugi
Apolipoprotein-8pecific High Densi~ Lipoprotein Populations
in Plasma of Carriers of the Apolipoprotein
AI-Ni 1811o. . . • • . • • • . • • • • • . . • . • . . • . • . . • • . • . • . • . • . • • . . • • . • • . • . • . . .• 67
A.V. Nichols, M.C. Cheung, P.J. Blanche, E.L. Gong,
G. Franceschini and C.R. Sirtori
APOLlPOPHOTEIN B
Apo B Gene Variants Are Involved in Determining Serum
Cholesterol Levels: towards Identifying these Variants •••••••••• 75
P. Talmud, R. Houlston, A. Dunning and S. Humphries
Genetic Evidence that the Apolipoprotein Gene Is not Involved
in Abetal ipoproteinemia. • • • • • • • • • • • • • • • • • • • • • • • • • • • • . • • • • • • • • • •• 81
P.J. Talmud, J. Lloyd, D. Muller, D.R. Collins,
J. Scott and S. Humphries
RFLPS of ApoB Gene. • • • • • • • • • • • • • • • • ... • • • • • • • • • • • • • • • • • • . • • • • • • • • • • • • •• 85
F. Turturro, J. Heibig, G.C. Ghisel1i and A.M. Gotto Jr.
Apo1ipoprotein B Genetic Deficiences ••••••••••••••••••••••.••••••••••. 95
R. Infante
APOLIPOPROTEIN C-II AND C-III
The Molecular Basis of Apo C-II Deficiency ••••••••••••••••.•••••••••• 109
8.8. Fojo, U. Beisiegel, A.F.H. 8talenhoef, M. Bojanovski,
R.E. Gregg, H. Greten and H.B. Brewer Jr.
Familial Chylomicronemia Due to "Mutations in Apolipoprotein
CII: Apolipoprotein CII-Toronto and
Apo1ipoprotein CII-St. Michael •••• "• •••••••••••••••••••••••••••• 121
P.W. Connelly, G.F. Maguire and J.A. Little
Apolipoprotein C-II Deficiency Syndrome: New Insights into the
Molecular Mechanism Leading to the Disease in the Apo
C-Ilp do Kindred ....•.........................•...•.....•....• 127
G. Bagg1~, ~ Fojo, C. Gabelli, S. Martini, L. Previato,
C. Corti, G. Crepaldi and H.B. Brewer Jr.
Biochemical Aspects and Molecular Study a Case of
Apo ell Deficit................................................ 137
G. Pepe. C. Crecchio, A. Tullo, A.M. Mogavero,
M. De Tommaso and A. Capurso
x
The Molecular Basis of the Defect in Familial Combined
Apolipoproteins AI and CIII Deficiency •••••.••••••.•.•••••.•••• 143
S.K. Karathanasis
Familial Apolipoprotein A-I, C-III and A-IV
Deficiency. • • • • • . • . • • • • • • • . . • . . • . • • . • • . . • • • . • . . • • • • • • • . • . • • • • .• 157
J.M. Ordovas, D.C. King and E.J. Schaefer
DYSLIPOPROTElNEMIAS, CORONARY ARTERY DISEASE AND DIABETES
Phenotypic Expression of Hepatic Lipase Deficiency ....•..••...••.•••. 161
P. Connelly, G. McGuire, M. Lee, R. McPherson
and A. Little
Abnormal Processing of HDL Precursors in Tangier
Monocyte Derived Macrophages .••••••.••••••••.•••••.•••••••••••. 167
G. Schmitz, H. Rob enek, B. Brennhausen and G. Assmann
Apo E Polymorphism in Relation to the Expression
of Familial Dysbetalipoproteinemia ••••..•.••.••.•••.••.•.•••.•• 175
L.M. Havekes, P. de Knijff, J .G. Leuven and R.R. Frants
Identification of an Italian Kindred with a Variant
Apolipoprotein E (E1) Associated with Type
III Hyperlipoproteinemia .••.•....•••...•.•.•....••..•.•.•.....• 181
C. Gabelli, G. Baggio, A. Pagnan, G. Zanetti, G.M.
Barbato, S. Martini, C. Bilato, C. Corti and G. Crepaldi
Normolipidemic Dyslipoproteinemia in Patients with
Coronary Artery Disease........................................ 189
G. Ghiselli, E. Wittels, J. Heibig and A.M. Gotto Jr.
Current Status on the Apo E-Receptor .•••..•••..•.•...••.••.•.•.••••• 207
U. Beisiegel, G. Ihrke, W. Weber, P. Lohse and H. Greten
DNA Polymorphisms of the Glucose Transporter Gene
in non-Insulin Dependent Diabetes Mellitus (NIDDM) •.••.••••.••• 211
S. Li and D.J. Galton
LIPOPROTEIN STRUCTURE: IMMUNOLOGICAL METHODS
Computer-Modelling of Human Apolipoproteins and of their
Mutants ••••••••••••••.••••••••••.•••.•.••.•••••.•••.•.••..••..• 215
M. Rosseneu, J .M. Ruysschaert and M. Froeyen
Monoclonal Antibodies to Human Apolipoprotein A-I •••••••.••.••.•.••• 221
A.L. Catapano and S. Marcovina
xi