Inherited quantitative DNA variation in the LPA (“apolipoprotein (a)”) gene

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Abstract
The Lp(a) antigen resides in a polypeptide chain that is attached to apolipoprotein B (apoB) by a disulfide bridge. Recently, cDNA for this polypeptide chain (frequently referred to as the Lp(a) polypeptide chain, Lp(a) apolipoprotein or apolipoprotein (a)) was cloned and extensive homology to plasminogen was uncovered. This homology creates significant difficulties in studying DNA variation in the gene (the LPA gene) for this polypeptide and the plasminogen gene. We have studied a variant 2 kilobase (kb) DNA fragment detectable after digestion with the restriction enzyme MspI, which appears to originate from the LPA gene since it is detected by LPA probes but not with plasminogen probes. It is related to the "kringle IV" region of the LPA gene since it is detected with an LPA probe that only contains "kringle IV" repeats. A proportion of people appears to lack (or have an undetectable level of) the 2 kb fragment and there are significant quantitative differences between samples from people who have the fragment. Presence and amount of this fragment appear to segregate in families as a Mendelian trait. This quantitative DNA variation is likely to reflect differences between individuals in number of "kringle IV" repeats at the LPA locus.