Association of mutations in the apolipoprotein B gene with hypercholesterolemia and the risk of ischemic heart disease

被引:154
作者
Tybjaerg-Hansen, A
Steffensen, R
Meinertz, H
Schnohr, P
Nordestgaard, BG
机构
[1] Univ Copenhagen, Herlev Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark
[2] Univ Copenhagen, Rigshosp, Natl Univ Hosp, Dept Med B,Div Cardiol, DK-2100 Copenhagen, Denmark
[3] Univ Copenhagen, Rigshosp, Natl Univ Hosp, Copenhagen City Heart Study, DK-2100 Copenhagen, Denmark
关键词
D O I
10.1056/NEJM199805283382203
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Familial hypercholesterolemia leads to premature ischemic heart disease and is often caused by mutations in the gene for the low-density lipoprotein receptor. Mutations in the apolipoprotein B gene, which encodes a ligand for this receptor, may also result in this phenotype, Methods We studied the genotypes of 9255 women and men from the general population, 948 patients with ischemic heart disease, and 36 patients with familial hypercholesterolemia, all from Denmark, for three mutations in the apolipoprotein B gene: Arg3500Gln, Arg3531Cys, and Arg3500Trp. Results The prevalence of heterozygotes in the general population was 0.08 percent (95 percent confidence interval, 0.03 to 0.16 percent) for both the Arg3500Gln and the Arg3531Cys mutations, and 0.00 percent (95 percent confidence interval, 0.00 to 0.18 percent) for the Arg3500Trp mutation. Among carriers of the Arg3500Gln mutation, cholesterol levels were significantly higher than among noncarriers in the general population - by 100 mg per deciliter (2.6 mmol per liter) among carriers in the general population, 154 mg per deciliter (4.0 mmol per liter) among patients with ischemic heart disease, and 172 mg per deciliter (4.5 mmol per liter) among patients with familial hypercholesterolemia. Heterozygous carriers of the Arg3500Gln mutation were significantly more common among patients with ischemic heart disease (odds ratio, 7.0; 95 percent confidence interval, 2.2 to 22; P=0.003) and patients with familial hypercholesterolemia (odds ratio, 78; 95 percent confidence interval, 16 to 388; P=0.001) than in the general population. Heterozygous carriers of the Arg3531Cys mutation in the general population did not have higher-than-normal plasma cholesterol levels or an increased risk of ischemic heart disease (odds ratio; 1.4; 95 percent confidence interval, 0.2 to 11; P=0.54), Conclusions The Arg3500Gln mutation in the apolipoprotein B gene, which is responsible for familial defective apolipoprotein B-100 and is present in approximately 1 in 1000 persons in Denmark, causes severe hypercholesterolemia and increases the risk of ischemic heart disease. (C) 1998, Massachusetts Medical Society.
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页码:1577 / 1584
页数:8
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