Associations of allelic differences at the A-I/C-III/A-IV gene cluster with carotid artery intima-media thickness and plasma lipid transport in hypercholesterolemic-hypertriglyceridemic humans.

Abstract

Individuals with elevated levels of plasma cholesterol and triglyceride may be at higher risk for coronary artery disease than those with isolated elevations of either cholesterol or triglyceride. Sequence variation in the A-I/C-IH/A-IV gene cluster has been implicated in the etiology of some disorders associated with premature atherosclerosis and/or hypertriglyceridemias with or without elevations of cholesterol. This led to the hypothesis that allelic variation at this gene locus alters plasma lipid transport and affects susceptibility for atherosclerosis. The study population, from the Atherosclerosis Risk in Communities (ARIC) Study, consisted of 50 normolipidemic individuals, 48 subjects with elevated plasma cholesterol, 47 subjects with elevated plasma triglyceride, and 123 subjects with both elevated plasma cholesterol and triglyceride who were used to evaluate associations between an Xmn I polymorphic site 2.5 kilobase pairs (kbp) upstream of the structural gene for apolipoprotein (apo) A-I, intimal-medial thickening of the extracranial carotid arteries, and several plasma lipid factors. The relative allele frequencies of the 8.3-kbp allele and the 6.6-kbp allele were .86

The genetic background modifies the effects of the obesity mutation, ‘fatty’, on apolipoprotein gene regulation in rat liver

“…In humans allelic variation in this complex has been associated with hyperlipoproteinaemia, 4 with hypertriglyceridaemia in obesity, 5 with the response of plasma lipid levels to diet, 6 and with atherosclerotic disease. 7 ApoA-IV is a component of triglyceride-rich lipoproteins, of HDL, and of the lipoprotein free plasma fraction. Both apoA-IV and apoA-I, the main protein constituent of HDL, participate in reverse cholesterol transport and confer protection against atherosclerosis.…”

Haplotypes of the ApoA-I/C-III/A-IV Gene Cluster and Familial Combined Hyperlipidemia

“…An association between FCHL and an XmnI restriction fragment polymorphism in the 5Ј-flanking region of the apoA-I gene was reported, 12 and the finding was later confirmed by linkage (logarithm of the odds [lod] score, 6.86) without recombinants in 7 families. 13 Further evidence for an association between this gene cluster and FCHL has been provided by other groups, 14 -16 but the findings have also been challenged, [17][18][19][20] and the positive linkage result has not been confirmed. An explanation for this controversy may be provided by a recent study, 21 in which the contribution of the apoA-I/C-III/A-IV gene cluster is presented as an epistatic interaction between different haplotypes, a finding that may also partially explain the paradigm of the complex and varying phenotypes of FCHL.…”

Genome-Wide Linkage Analysis of Lipids in the Hypertension Genetic Epidemiology Network (HyperGEN) Blood Pressure Study

“…Key Words: genome scan Ⅲ lipids Ⅲ cholesterol Ⅲ triglyceride Ⅲ genetic linkage S erum lipoprotein-lipid levels are major risk factors for coronary heart disease, 1 and genes involved in lipoprotein metabolism have been implicated in coronary heart disease. [2][3][4] Discovery of the genetic determinants of quantitative variation in lipid levels could help to elucidate the genetics of coronary heart disease.Studies have indicated that lipid levels are significantly heritable. Point estimates of heritability for total cholesterol, HDL cholesterol (HDL-C), and plasma triglycerides (TGs) range from 42% to 65%, 45% to 83%, and 37% to 75%, respectively, with twin studies providing higher point estimates.…”

“…Key Words: genome scan Ⅲ lipids Ⅲ cholesterol Ⅲ triglyceride Ⅲ genetic linkage S erum lipoprotein-lipid levels are major risk factors for coronary heart disease, 1 and genes involved in lipoprotein metabolism have been implicated in coronary heart disease. [2][3][4] Discovery of the genetic determinants of quantitative variation in lipid levels could help to elucidate the genetics of coronary heart disease.…”

“…[2][3][4] Discovery of the genetic determinants of quantitative variation in lipid levels could help to elucidate the genetics of coronary heart disease.…”