F ive distinct polymorphic sites on the structural gene for human apolipoprotein B (apo B) are responsible for the major antigenic polymorphisms of plasma low density lipoproteins (LDL); together, these epitopic sites constitute the system of Ag determinants. 123 Since each of the five sites encodes two alternative amino acid sequences, there exist a total of ten Ag epitopes associated with the apo B potypeptkje which may be arranged in five allelic pairs: Ag(c/g), Ag(a1/d), Ag(h/i), Ag(x/y), and Ag(t/z). Recently an association was reported between a restriction fragment length polymorphism (RFLP) detected by restriction enzyme Xba I and the Ag(c/g) epitopic site. 4 The phenotypes predicted with the Xba I RFLP were identical to those predicted with the Ag(g/c) determinant in 14 of the 17 cases examined (p<0.001). On the other hand, the same RFLP was reportedly significantly (p<0.03) associated with a different Ag locus, Ag(x/y), in a separate study involving 75 unrelated individuals that was conducted by Berg et al. We have performed a more extensive study on the relationship between the Xba I RFLP and the two Ag sites, Ag(c/g) and Ag(x/y) using 106 individuals. In this communication, we report that the Xba I RFLP of apo B is associated with both the Ag(c/g) and the Ag(x/y) sites. All of theXbal(X1/X1) phenotypes examined in this study are Ag(y/y), while most of the Xba I(X2) alleles appear to be Ag(g). We also show that these data are explained by the existence of four major alleles associated with human apo B, although other minor alleles must exist.Lending additional interest are studies providing evidence both for and against an association between human apo B polymorphisms and serum lipid and apo B levels and myocardial infarction. 6 -12 In the studies reported here, however, no statistically significant differences in lipid levels were found to be associated with any of the apo B alleles.
Methods
Study PopulationThe Johns Hopkins University Coronary Artery Disease (JHU-CAD) Study is a consecutive case study of men ages 50 years or less and of women ages 60 years or less who were undergoing elective nonemergency coronary arteriography at The Johns Hopkins Hospital. The spouses of the index cases were also studied. In all, 47 male index cases, 29 female index cases, 6 male spouses, and 24 female spouses were included in our sample. The details of the study will be published elsewhere, but the pertinent information is briefly summarized here. After informed consent, each index case had a medical and family history and brief physical examination. After an overnight fast of at least 12 hours,