A DNA insertion in the apolipoprotein A-I gene of patients with premature atherosclerosis.

Apolipoprotein A-I (apo A-I) is the major protein constituent of high-density lipoprotein (HDL). The study of the apo A-I gene is of interest because plasma levels of HDL have been inversely correlated with the development of coronary artery disease and because polymorphisms related to this gene have been associated with hypertriglyceridaemia and premature atherosclerosis. We have recently isolated and characterized the human apo A-I gene and have shown that apo A-I and apolipoprotein C-III (apo C-III) genes are physically linked and that a polymorphism (of unknown frequency in the general population) of the apo A-I gene is inherited as a mendelian trait linked to premature atherosclerosis in an affected family (not the same polymorphism as has previously been reported to be associated with hypertriglyceridaemia). Here we report that this polymorphism is due an at least 6.5-kilobase (kb) DNA insertion in the coding region of the apo A-I gene and that there is no detectable alteration (as determined by limited genomic blotting analysis) of the apo C-III gene of these patients.