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

Abstract

Apolipoprotein A-I (apo A-I) is the major protein constituent of high-density lipoprotein (HDL)¹. 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 disease² and because polymorphisms related to this gene have been associated with hypertriglyceridaemia³ and premature atherosclerosis^4,5. We have recently isolated and characterized the human apo A-I gene⁶ and have shown that apo A-I and apoliprotein C-III (apo C-III) genes are physically linked⁷ 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 family⁵ (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.