Severe hyperlipidemia in apolipoprotein E2 homozygotes due to a combined effect of hyperinsulinemia and an SstI polymorphism

Citation
Ej. Sijbrands et al., Severe hyperlipidemia in apolipoprotein E2 homozygotes due to a combined effect of hyperinsulinemia and an SstI polymorphism, ART THROM V, 19(11), 1999, pp. 2722-2729
Citations number
63
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
10795642 → ACNP
Volume
19
Issue
11
Year of publication
1999
Pages
2722 - 2729
Database
ISI
SICI code
1079-5642(199911)19:11<2722:SHIAEH>2.0.ZU;2-T
Abstract
More than 90% of patients with type III hyperlipoproteinemia are homozygous carriers of the apolipoprotein (apo) E*2 allele. The great majority of the se apoE2(Arg158-->Cys) homozygotes in the general population, however, are normolipidemic. Apparently, expression of the hyperlipidemic state requires additional genetic and/or environmental factors, suggesting a multifactori al etiology. To elucidate these additional risk factors, we analyzed normol ipidemic and hyperlipidemic apoE2 homozygotes. Hyperinsulinemia was observe d in 27 of 49 apoE2 homozygotes and associated with elevated lipid levels: hyperinsulinemic apoE2 homozygotes had type III hyperlipoproteinemia 6 time s more often than apoE2 homozygotes with normal insulin levels (odds ratio 6.2, P = 0.02). We screened the normolipidemic and hyperlipidemic apoE2 hom ozygotes for common variants in candidate genes involved in lipolysis-the A POA1-C3-A4 gene cluster, lipoprotein lipase, and hepatic lipase-and analyze d for associations with the expression of hyperlipidemia. In the hyperinsul inemic group, the 7 carriers of the SstI polymorphism (S2) in the APOC3 gen e displayed severely elevated VLDL cholesterol (P-insulin by SstI<0.001) an d VLDL triglyceride (P-insulin by SstI<0.01) and low levels of HDL (P-insul in by SstI<0.02) In the normoinsulinemic group, no such relation of the Sst I polymorphism with hyperlipidemia was observed. These data provide the fir st evidence for a combined effect of hyperinsulinemia and the SstI polymorp hism on the expression of hyperlipidemia in apoE2 homozygotes.