A Genetic Marker in the Apolipoprotein AI/CIII Gene Complex Associated with Hypercholesterolaemia

Abstract

In 1983 we reported a strong association between hypertriglyceridaemia and a restriction fragment length polymorphism (RFLP) associated with the apolipoprotein AI gene which was not present in normolipidaemic individuas (Rees et al. 1983). This RFLP arises because of the existence of a polymorphic nucleotide in the 3’ non-coding region of the linked apo-CIII gene that creates an additional cleavage site for the restriction enzyme SacI (Shoulders and Baralle 1986). Since our original observation, two groups have reported a significant increase in the incidence of the variant apo-AI/CIII allele (S2) in patients with severe coronary heart disease (CHD), and in survivors of myocardial infarction compard with healthy controls (Ferns et al. 1985; Rees et al. 1985). However, this increased frequency could not entirely be explained by a greater number of hypertriglyceridaemic individuals in these groups. In view of these observations and the fact that Kessling and Humphries (1985) could not confirm our initial findings (Rees et al. 1983), we have tried to clarify the relationship between the S2 allele and hyperlipidaemia by studying newly recruited patients with well-definied forms of hyperlipidaemia.