edoc

Differences in the phenotypic characteristics of subjects with familial defective apolipoprotein B-100 and familial hypercholesterolemia

Miserez, A. R. and Keller, U.. (1995) Differences in the phenotypic characteristics of subjects with familial defective apolipoprotein B-100 and familial hypercholesterolemia. Arteriosclerosis, thrombosis, and vascular biology, Vol. 15, H. 10. S. 1719-1729.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6419941

Downloads: Statistics Overview

Abstract

Familial defective apolipoprotein B-100 (FDB) is a recently identified autosomal-dominantly inherited disorder caused by a point mutation in the apolipoprotein (apo) B gene. To determine whether the phenotypic characteristics in FDB subjects are similar to those in subjects with familial hypercholesterolemia (FH), 76 kindreds fulfilling the clinical criteria for heterozygous FH/FDB were characterized using molecular biological techniques. Allele-specific polymerase chain reaction (PCR) at the apoB locus was used for diagnosis or exclusion of FDB. PCR-based methods for detection of two point mutations (V408M and P664L) at the LDL receptor (LDLR) locus, cosegregation analysis using eight restriction fragment length polymorphisms (RFLPs) at the LDLR locus, or the exclusion of FDB confirmed the clinical diagnosis of FH. Three kindreds were not included because of a missing cosegregation between a particular haplotype and the FH phenotype. We predicted that a similar number of kindreds would be detected in the two groups, assuming comparable prevalences of the diseases in our population and similar phenotypic characteristics. However, only nine kindreds were identified with the FDB mutation compared with 64 kindreds with FH (P textless .0001). From these 73 kindreds, 28 FDB heterozygotes and 129 FH heterozygotes were compared using multivariate analysis. There were no differences between these two groups with respect to age, sex, and apoE genotype distribution, lipoprotein(a) concentrations, body mass index, blood pressure, and smoking habits. However, FDB subjects demonstrated significantly lower concentrations of total cholesterol (8.1 versus 10.2 mmol/L, P textless .001), LDL cholesterol (6.3 versus 8.2 mmol/L, P textless .001), and triglycerides (1.3 versus 1.8 mmol/L, P = .025) and higher concentrations of HDL cholesterol (1.4 versus 1.2 mmol/L, P = .015) than subjects with FH. In contrast to FH, female FDB subjects tended to have higher concentrations of tot cholesterol (8.9 versus 7.5 mmol/L, P = .032) and LDL cholesterol (7.1 versus 5.7 mmol/L, P = .026) than FDB males. The same results regarding total and LDL cholesterol and sex differences were observed when individual data of 238 FDB and 415 FH subjects from the literature were compared. In addition, FDB subjects showed much larger total cholesterol fluctuations than FH subjects (median of intraindividual coefficients of variation: FDB, 14.5%; FH, 5.3%; P textless .001). In summary, these results demonstrate that FDB subjects tend to have a milder form of hyperlipoproteinemia than FH subjects and that only a part of the subjects with FDB fulfill the established criteria for identifying FH.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Metabolism (Keller/Müller)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Klinische Endokrinologie (Keller)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Klinische Endokrinologie (Keller)
UniBasel Contributors:Keller, Ulrich O.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:American Heart Association
ISSN:1079-5642
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:02 Oct 2015 10:00
Deposited On:02 Oct 2015 10:00

Repository Staff Only: item control page