Aouizerat B E, Allayee H, Cantor R M, Davis R C, Lanning C D, Wen P Z, Dallinga-Thie G M, de Bruin T W, Rotter J I, Lusis A J
Departments of 1Microbiology and Molecular Genetics, Medicine, Human Genetics, Molecular Biology Institute, University of California, UCLA School of Medicine Los Angeles, CA 90095-1679, USA.
Am J Hum Genet. 1999 Aug;65(2):397-412. doi: 10.1086/302490.
Familial combined hyperlipidemia (FCHL) is a common familial lipid disorder characterized by a variable pattern of elevated levels of plasma cholesterol and/or triglycerides. It is present in 10%-20% of patients with premature coronary heart disease. The genetic etiology of the disease, including the number of genes involved and the magnitude of their effects, is unknown. Using a subset of 35 Dutch families ascertained for FCHL, we screened the genome, with a panel of 399 genetic markers, for chromosomal regions linked to genes contributing to FCHL. The results were analyzed by use of parametric-linkage methods in a two-stage study design. Four loci, on chromosomes 2p, 11p, 16q, and 19q, exhibited suggestive evidence for linkage with FCHL (LOD scores of 1.3-2.6). Markers within each of these regions were then examined in the original sample and in additional Dutch families with FCHL. The locus on chromosome 2 failed to show evidence for linkage, and the loci on chromosome 16q and 19q yielded only equivocal or suggestive evidence for linkage. However, one locus, near marker D11S1324 on the short arm of human chromosome 11, continued to show evidence for linkage with FCHL, in the second stage of this design. This region does not contain any strong candidate genes. These results provide evidence for a candidate chromosomal region for FCHL and support the concept that FCHL is complex and heterogeneous.
家族性混合性高脂血症（FCHL）是一种常见的家族性脂质紊乱疾病，其特征是血浆胆固醇和/或甘油三酯水平升高的模式各不相同。在早发性冠心病患者中，该病的发生率为10%-20%。该病的遗传病因，包括涉及的基因数量及其作用大小，尚不清楚。我们使用为FCHL确诊的35个荷兰家族的一个子集，用一组399个遗传标记对基因组进行筛选，以寻找与导致FCHL的基因相关的染色体区域。在两阶段研究设计中，使用参数连锁方法对结果进行分析。在2号染色体、11号染色体、16号染色体和19号染色体上的四个位点显示出与FCHL连锁的提示性证据（LOD得分为1.3-2.6）。然后在原始样本和其他患有FCHL的荷兰家族中检查这些区域内的标记。2号染色体上的位点未显示出连锁证据，16号染色体和19号染色体上的位点仅产生了模棱两可或提示性的连锁证据。然而，在该设计的第二阶段，位于人类11号染色体短臂上标记D11S1324附近的一个位点继续显示出与FCHL连锁的证据。该区域不包含任何强候选基因。这些结果为FCHL的一个候选染色体区域提供了证据，并支持FCHL是复杂且异质性的这一概念。
