在不同背景人群中鉴定出的低密度脂蛋白受体突变杂合子的表型。

Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations.

作者信息

Tybjaerg-Hansen Anne, Jensen Henrik Kjaerulf, Benn Marianne, Steffensen Rolf, Jensen Gorm, Nordestgaard Børge G

机构信息

Department of Clinical Biochemistry KB 3011, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.

出版信息

Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):211-5. doi: 10.1161/01.ATV.0000149380.94984.f0. Epub 2004 Nov 4.

DOI:10.1161/01.ATV.0000149380.94984.f0

PMID:15528480

Abstract

BACKGROUND

The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population and type of mutation (LDL receptor [LDLR] or APOB R3500Q) for cholesterol phenotype.

METHODS AND RESULTS

We studied 9255 individuals from the general population, 948 patients with ischemic heart disease (IHD), and 63 patients with clinical familial hypercholesterolemia (FH) for 3 common LDL receptor mutations. Average increase in cholesterol in LDL receptor heterozygotes identified in the general population or among patients with IHD or FH compared with noncarriers was 2.9 mmol/L, 4.1 mmol/L, and 4.9 mmol/L, respectively (P=0.02). Background population and type of mutation determined cholesterol phenotype; average increase in LDL cholesterol from carriers in the general population to carriers with clinical FH was 1.6 mmol/L (P=0.03). The average increase for carriers of LDLR mutations compared with carriers of APOB R3500Q was 1.2 mmol/L (P=0.05).

CONCLUSIONS

The phenotype associated with a given mutation should not be determined in patients, but rather in unselected individuals in the general population.

摘要

背景

由于确诊偏倚，突变对表型的影响常常被高估。我们确定了背景人群对与低密度脂蛋白（LDL）受体特定突变相关的胆固醇表型的影响，以及背景人群和突变类型（LDL受体[LDLR]或APOB R3500Q）对胆固醇表型的相对重要性。

方法与结果

我们研究了来自普通人群的9255人、948例缺血性心脏病（IHD）患者和63例临床家族性高胆固醇血症（FH）患者的3种常见LDL受体突变。与非携带者相比，在普通人群、IHD患者或FH患者中鉴定出的LDL受体杂合子的胆固醇平均升高分别为2.9 mmol/L、4.1 mmol/L和4.9 mmol/L（P=0.02）。背景人群和突变类型决定胆固醇表型；从普通人群中的携带者到临床FH携带者，LDL胆固醇的平均升高为1.6 mmol/L（P=0.03）。与APOB R3500Q携带者相比，LDLR突变携带者的平均升高为1.2 mmol/L（P=0.05）。