Physiological Reviews, Vol 68, 85-132, Copyright © 1988 by American Physiological Society
Apolipoprotein genetic variation and human disease
J. L. Breslow
Rockefeller University, New York, New York.
Atherosclerosis is the major public health problem in much of the world
today. The information summarized in this review, based on the recognized
apolipoprotein structural variants appreciated at both the protein and gene
levels, indicates that apolipoprotein genetic variation plays a major role
in determining human genetic susceptibility to this disease. With the use
of cloned apolipoprotein genes, it should, in the near future, be possible
to determine how their expression is regulated; this should provide insight
into other classes of mutations of a regulatory nature that might have
clinical significance. In addition, the many association and linkage
studies currently being undertaken will provide the rationale for cloning
defective alleles and determining specific causative mutations. Both
structural and regulatory mutations can then be described either with
restriction enzymes and Southern blotting or by direct oligonucleotide
hybridization techniques in the general population. This will allow the
identification of presymptomatic atherosclerosis-susceptible individuals
who would be targets for primary preventative therapy.
