title: Genetic factors influencing apolipoprotein AI and AII levels in a kindred with premature coronary heart disease.
abstract: A single 51-member kindred, ascertained on the basis of a normotriglyceridemic proband with depressed high-density lipoprotein cholesterol (HDL-C) and myocardial infarctions at ages 40 and 42, was studied with respect to quantitative variation in HDL-C and apolipoprotein (apo) AI and AII levels. The results of bivariate segregation analysis suggest that the etiology of depressed HDL-C involves one or possibly two major loci: one has a pleiotropic effect on apo AI and apo AII levels and, possibly another one that affects apo AI levels. Both the major loci were characterized as having a dominant allele leading to depression of the respective trait(s). In addition, analysis of the cosegregation of HDL-C and apo AI levels gave evidence of residual nonfamilial factors common to both traits, leading to a positive covariance between them. This could reflect the role of apo AI in the transformation of nascent HDL-C particles into mature ones via its cofactor activity to lecithin cholesterol acyltransferase. The proposed two-locus model represents one possible etiology for the heterogeneous disorder of hypoalphalipoproteinemia. This analysis of a single pedigree does not completely define the genetic mechanism, but it does illustrate a useful new analytic approach.
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis.
authors.forename: I B
authors.initials: IB
authors.lastname: Borecki
authors.forename: P
authors.initials: P
authors.lastname: Laskarzewski
authors.forename: D C
authors.initials: DC
authors.lastname: Rao
mesh_terms: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A / Q000097:blood* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D004777:Environment; D005192:Family Health; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008957:Models, Genetic
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A; D008076:Cholesterol, HDL