Koivisto U M, Hämäläinen L, Taskinen M R, Kettunen K, Kontula K
Institute of Biotechnology, University of Helsinki, Finland.
J Lipid Res. 1993 Feb;34(2):269-77.
Two deletions of the low density lipoprotein (LDL) receptor gene account for about 90% of the mutations that cause familial hypercholesterolemia (FH) in eastern Finland. The FH-Helsinki mutation deletes exons 16, 17 and a portion of exon 18, while the FH-North Karelia allele is characterized by a deletion of seven nucleotides from exon 6 of the LDL receptor gene. We developed a DNA assay based on the use of polymerase chain reaction (PCR) which simultaneously detects both of these mutations. We have screened 90 young (< 45 years) eastern Finns with symptomatic coronary heart disease (CHD) for the presence of these FH genes. One or the other of the mutations was present in 4 out of 55 survivors of acute myocardial infarction (AMI) and 4 out of 35 patients with angina pectoris (AP), but in none of 50 healthy controls of similar age. These data show a relatively high prevalence of confirmed FH in young CHD patients (AMI and MI combined: 8/90, or 9%), and also demonstrate the feasibility of PCR techniques in diagnosis of FH among populations with enrichment of specific types of LDL receptor gene mutations.
在芬兰东部,低密度脂蛋白(LDL)受体基因的两种缺失突变约占导致家族性高胆固醇血症(FH)的突变的90%。FH - 赫尔辛基突变缺失了第16、17外显子以及第18外显子的一部分,而FH - 北卡累利阿等位基因的特征是LDL受体基因第6外显子缺失7个核苷酸。我们开发了一种基于聚合酶链反应(PCR)的DNA检测方法,可同时检测这两种突变。我们对90名患有症状性冠心病(CHD)的芬兰东部年轻人(<45岁)进行了筛查,以确定他们是否存在这些FH基因。在55名急性心肌梗死(AMI)幸存者中有4人、35名心绞痛(AP)患者中有4人存在其中一种突变,但在50名年龄相仿的健康对照者中均未发现。这些数据表明,在年轻的CHD患者中确诊的FH患病率相对较高(AMI和AP患者合并:8/90,即9%),同时也证明了PCR技术在富含特定类型LDL受体基因突变的人群中诊断FH的可行性。