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Significant hypertriglyceridemia with a very marked decrease of high density lipoproteins (HDL)-cholesterol levels (7-14 mg/dl) was detected in three members (father, son, and daughter) of an Italian family. The three affected individuals did not show any clinical signs of atherosclerosis, nor was the atherosclerotic disease significantly present in the family. Lipoprotein lipase and lecithin:cholesterol acyltransferase activites were normal or slightly reduced. Morphological and compositional studies of HDL in the subjects showed a significant enlargement of the lipoprotein particles (approximately 120 vs. approximately 94 A for control HDL) and a concomitant increase in the triglyceride content. Analytical isoelectric focusing of HDL apoproteins provided evidence for multiple isoproteins in the apoprotein(apo)-A-I range, with nine different bands being detected instead of the usual four bands observed in normal subjects. Two-dimensional immunoelectrophoresis against apo-A antiserum indicated a clear reduction of apo-A in the alpha electrophoretic region, with splitting of the protein "peak." The observation in otherwise clinically healthy subjects of hypertriglyceridemia, reduced HDL-cholesterol, and marked apoprotein abnormalities, without a significant incidence of atherosclerotic disease in the family suggests this is a new disease entity in the field of lipoprotein pathology, very probably related to an altered amino acid composition of the apo-A-I protein (see Weisgraber et al. 1980. J. Clin. Invest. 66: 901-907).

the journal of clinical investigation/the journal of clinical investigation

A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family.