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We are studying the genetic factors underlying the common forms of heart disease by Identifying genes that affect normal variations in plasma llpid, lipoproteln, and apolipoprotein concentrations In baboons. For these studies we are using cloned human gene probes to Identify restriction fragment length polymorphisms (RFLPs) at loci encoding the proteins of cholesterol metabolism. In this report we present the Identification and mapping of a polymorphic Ava II cleavage site In Intron 17 of the baboon low density lipoprotein (LDL) receptor gene. We determined genotypes for this RFLP on a population of 253 pedigreed baboons and assessed the effect of LDL receptor RFLP genotypes on serum concentrations of LDL cholesterol (LDL-C) and apolipoprotein B (apo B). These measures were obtained for each baboon on each of two diets: a low cholesterol, low fat (basal) diet and a high cholesterol, high saturated fat (atherogenlc) diet Statistical analysis detected a significant association between LDL receptor genotype and serum LDL-C and apo B concentrations on both diets. Homozygotes for the rarer allele had lower serum concentrations of LDL-C and apo B than did homozygotes for the common allele, and with the exception of apo B levels on the basal diet, Intermediate levels were observed in heterozygotes. The LDL receptor RFLP accounted for approximately 3% to 7% of the variation In serum LDL-C and apo B concentrations on both diets.
Arteriosclerosis – Wolters Kluwer Health
Published: Nov 1, 1989
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