title: The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals.
abstract: Recent advances in molecular biology provide measures of genotypes at loci involved in lipid metabolism. Genotypes for apolipoprotein E (apo E) and quantitative levels of total plasma cholesterol, betalipoprotein, and triglycerides were measured in a sample of 223 unrelated individuals from Nancy, France. The frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles are 0.13, 0.74, and 0.13, respectively, in this sample. Significant differences among apo E genotypes were detected for these lipoprotein phenotypes. The average effect of the epsilon 2 allele was to reduce total plasma cholesterol and betalipoprotein levels by 0.52 mmol/L and 0.98, respectively, while the epsilon 4 allele raised these levels by 0.26 mmol/L and 0.61, respectively. Apo E genotype specific correlations suggest that this locus also has an effect on the coordinated metabolism between cholesterol and triglycerides. We infer that approximately 17% of the genetic variability in total plasma cholesterol may be attributable to this apo E polymorphism. No other single locus has been identified with such a large contribution to cardiovascular disease risk factors in the general population.
mesh_terms: D000483:Alleles; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D001161:Arteriosclerosis / Q000235:genetics; D002784:Cholesterol / Q000097:blood*; D005602:France; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012306:Risk; D013223:Statistics as Topic; D014280:Triglycerides / Q000097:blood*
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol