TY - JOUR
T1 - 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
AU - Patsch, Wolfgang
AU - Richey Sharrett, A.
AU - Chen, Iou Y.
AU - Lin-Lee, Yen Chiu
AU - Brown, Spencer A.
AU - Gotto, Antonio
AU - Boerwinkle, Eric
PY - 1994
Y1 - 1994
N2 - 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-III/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 and .14, respectively, in the entire study population and did not differ among the lipid phenotypes. In the group with elevated plasma cholesterol and triglyceride, subjects possessing the 6.6-kbp allele exhibited a greater carotid artery intimal-medial thickness (P=.034) and higher plasma levels of apoA-I, high-density lipoprotein (HDL) cholesterol, and HDL3 cholesterol (P<.02) than subjects homozygous for the 8.3-kbp allele. In contrast, subjects with the 6.6-kbp allele displayed lower mean ratios of apolipoproteins C-II to C-III, C-II to A-IV, and E to A-IV in plasma (P<.05) and a lower mean ratio of apolipoprotein C-II to C-III in the triglyceride-rich lipoproteins (P=.026). Sequence variation in or near the genes encoding apolipoproteins A-I, C-III, and A-IV may therefore identify a group of hypercholesterolemic-hypertriglyceridemic persons who are at higher risk for atherosclerosis than others with the same lipopro-tein phenotype.
AB - 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-III/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 and .14, respectively, in the entire study population and did not differ among the lipid phenotypes. In the group with elevated plasma cholesterol and triglyceride, subjects possessing the 6.6-kbp allele exhibited a greater carotid artery intimal-medial thickness (P=.034) and higher plasma levels of apoA-I, high-density lipoprotein (HDL) cholesterol, and HDL3 cholesterol (P<.02) than subjects homozygous for the 8.3-kbp allele. In contrast, subjects with the 6.6-kbp allele displayed lower mean ratios of apolipoproteins C-II to C-III, C-II to A-IV, and E to A-IV in plasma (P<.05) and a lower mean ratio of apolipoprotein C-II to C-III in the triglyceride-rich lipoproteins (P=.026). Sequence variation in or near the genes encoding apolipoproteins A-I, C-III, and A-IV may therefore identify a group of hypercholesterolemic-hypertriglyceridemic persons who are at higher risk for atherosclerosis than others with the same lipopro-tein phenotype.
KW - Apolipoproteins
KW - Carotid atherosclerosis
KW - Gene expression
KW - Hyperlipidemia
UR - http://www.scopus.com/inward/record.url?scp=0028179523&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028179523&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.14.6.874
DO - 10.1161/01.ATV.14.6.874
M3 - Article
C2 - 8199177
AN - SCOPUS:0028179523
SN - 1079-5642
VL - 14
SP - 874
EP - 883
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 6
ER -