From Ag phenotyping to molecular genetics: apolipoprotein B, serum lipid levels and coronary artery disease in Finland.

Abstract

The Ag polymorphisms of low density lipoproteins (LDL) were described in the 1960's (Allison & Blumberg 1961, Bütler 1967). The first report suggesting that they may be associated with serum lipid levels did not appear until 1976 (Berg et al. 1976). Out of the 10 populations studied, the Finnish population showed the most marked association between Ag(x —) phenotype and elevated serum cholesterol and triglyceride levels. After this, little progress was made for several years, possibly because Ag antibodies were available in very few laboratories. The introduction of monoclonal antibodies directed against apo B in the 1980's provided a novel means to detect immunophenotypes of LDL (for review, see Tikkanen 1987a,b). Later on, the associations between common DNA polymorphisms of apo B, and the immunogenetic polymorphisms detected with Ag and monoclonal antibodies were described (Berg et al. 1986, Ma et al. 1987, Ma et al. 1989, Wang et al. 1990. Xu et al. 1989, Dunning et al. 1991). Some of the studies carried out in Finland demonstrated associations between certain apo B polymorphisms and serum lipid levels, while some associations reported elsewhere were absent in Finnish individuals. We explored the possibility that variation at the apo B gene locus contributed to the common occurrence of hyperlipidemias and coronary heart disease (CHD) among the Finns.