Title
Expression of type III hyperlipoproteinemia in apolipoprotein E2 (Arg158→Cys) homozygotes is associated with hyperinsulinemia
Author
de Beer, F.
Stalenhoef, A.F.H.
Hoogerbrugge, N.
Kastelein, J.J.P.
Leuven, J.A.G.
van Duijn, C.M.
Havekes, L.M.
Smelt, A.H.M.
Gaubius Instituut TNO
Publication year
2002
Abstract
Type III hyperlipoproteinemia (HLP) is mainly found in homozygous carriers of apolipoprotein E2 (apoE2, Arg158→Cys). Only a small percentage (<5%) of these apoE2 homozygotes develops hyperlipidemia, indicating that additional environmental and genetic factors contribute to the expression of type III HLP. In the present study, first, the prevalence of type III HLP among apoE2 homozygotes was estimated in a Dutch population sample of 8888 participants. Second, 68 normocholesterolemic and 162 hypercholesterolemic apoE2 homozygotes (type III HLP patients) were collected to investigate additional factors influencing type III HLP expression. In the Dutch population sample, apoE2 homozygosity occurred with a frequency of 0.6% (57 of 8888 individuals). Among the 57 E2/2 subjects, 10 type III HLP patients were identified (prevalence 18%). Comparison of normocholesterolemic E2/2 subjects and type III HLP patients showed that the latter had a significantly increased body mass index (25.6±4.0 versus 26.9±3.8 kg/m2, respectively; P=0.03) and prevalence of hyperinsulinemia (26% versus 63%, respectively; P<0.001). Multiple linear regression analysis demonstrated that most of the variability in type III HLP expression can be explained by fasting insulin levels (partial correlation coefficient ≈0.50, P<0.001). In contrast to men, apoE2 homozygous women aged ≥50 years had significantly higher plasma lipid levels than their counterparts aged <50 years. These data demonstrate that the expression of type III HLP in E2/2 subjects is elicited to a large extent by hyperinsulinemia. In addition, in female apoE2 homozygotes, the expression increases with age; this increase is most likely due to the loss of estrogen production. Chemicals/CAS: Apolipoprotein E2; Apolipoproteins E; Estrogens
Subject
Adult
Age of Onset
Aging
Apolipoprotein E2
Apolipoproteins E
Comorbidity
Coronary Disease
Estrogens
Female
Gene Expression
Gene Frequency
Homozygote
Humans
Hyperinsulinism
Hyperlipoproteinemia Type III
Male
Menopause
Middle Aged
Netherlands
Peripheral Vascular Diseases
Prevalence
Regression Analysis
Sex Factors
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DOI
https://doi.org/10.1161/hq0202.102919
TNO identifier
236467
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 22 (2), 294-299
Document type
article