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.
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.
Dept. of Internal Medicine, University of Genoa, Italy.
S
S
Bertolini
D A
DA
Coviello
P
P
Masturzo
E
E
Zucchetto
N
N
Elicio
R
R
Balestreri
G
G
Orecchini
S
S
Calandra
S
S
Humphries
D000328:Adult; D000368:Aged; D000483:Alleles; D001345:Autoradiography; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011973:Receptors, LDL / Q000235:genetics*; D012016:Reference Values
D008078:Cholesterol, LDL; D011973:Receptors, LDL