RFLPS OF THE LDL-RECEPTOR GENE - THEIR USE IN THE DIAGNOSIS OF FH AND IN EVALUATION OF DIFFERENT LEVELS OF GENE-EXPRESSION ON NORMAL SUBJECTS

被引：7

作者：

BERTOLINI, S

COVIELLO, DA

MASTURZO, P

ZUCCHETTO, E

ELICIO, N

BALESTRERI, R

ORECCHINI, G

CALANDRA, S

HUMPHRIES, S

机构：

[1] Atherosclerosis Prevention Centre - Dept. of Internal Medicine, University of Genoa, Genoa, 6 - 16132, Viale Benedetto XV

[2] Institute of Biology and Genetics, University of Genoa, Genoa, 6 - 16132, Viale Benedetto XV

[3] Institute of Clinical Medicine, University of Perugia, Perugia

[4] Institute of General Pathology, University of Modena

[5] The Centre for Genetics of Cardiovascular Disorders, The Rayne Institute London

来源：

EUROPEAN JOURNAL OF EPIDEMIOLOGY | 1992年 / 8卷

关键词：

FAMILIAL HYPERCHOLESTEROLEMIA; LDL-RECEPTOR GENE-POLYMORPHISM;

D O I：

10.1007/BF00145345

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

The usefulness of the RFLPs of the LDL-receptor gene in early diagnosis of Familial Hypercholesterolemia (FH) was investigated in 122 FH-families. Four RFLPs, produced by digestion with the enzymes PvuII, ApaLI and AvaII/XbaI were able to detect the affected gene and to follow the inheritance of the disease in 72 out of 97 families (74%). In the remaining 25 families, unambiguous diagnosis was possible in 66% of the cases by use of PvuII, ApaLI and BstEII/EcoRI RFLPs. The RFLPs were also useful to distinguish true homozygotes from compound heterozygotes and to detect families where recombination events occurred or where hypercholesterolemia was not due to a defect of the LDL-receptor gene. In a normal population PvuII RFLP account for 9.6% of the total variance of the LDL cholesterol levels adjusted for confounding variables. The P2 allele was associated with lower LDL cholesterol concentrations (average excess -9.1 mg/dl). This finding allows us to presume there is a DNA sequence, close to the variable PvuII cutting site in intron 15, which could act as an enhancer of the LDL-receptor gene expression.

引用

页码：18 / 25

页数：8

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