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Titolo:
Severe hyperlipidemia in apolipoprotein E2 homozygotes due to a combined effect of hyperinsulinemia and an SstI polymorphism
Autore:
Sijbrands, EJ; Hoffer, MJV; Meinders, AE; Havekes, LM; Frants, RR; Smelt, AHM; De Knijff, P;
Indirizzi:
Leiden Univ, Med Ctr, Fac Med, Dept Gen Internal Med, Leiden, Netherlands Leiden Univ Leiden Netherlands pt Gen Internal Med, Leiden, Netherlands Leiden Univ, Med Ctr, MGC, Dept Human Genet, Leiden, Netherlands Leiden Univ Leiden Netherlands C, Dept Human Genet, Leiden, Netherlands TNO, PG, Gaubius Lab, Leiden, Netherlands TNO Leiden NetherlandsTNO, PG, Gaubius Lab, Leiden, Netherlands
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 11, volume: 19, anno: 1999,
pagine: 2722 - 2729
SICI:
1079-5642(199911)19:11<2722:SHIAEH>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL COMBINED HYPERLIPIDEMIA; HEPATIC LIPASE GENE; DENSITY-LIPOPROTEIN CHOLESTEROL; INSULIN-RESISTANCE; MYOCARDIAL-INFARCTION; C-III; ENDOTHELIAL LIPASE; RECEPTOR-BINDING; HYPERTRIGLYCERIDEMIA; PROMOTER;
Keywords:
apolipoprotein E; hyperlipoproteinemia type III; hyperinsulinemia; xanthomas;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Sijbrands, EJ Acad Med Ctr, Dept Gen Internal Med, C-O Overtoom 49, NL-1054 HB Amsterdam, Netherlands Acad Med Ctr C-O Overtoom 49 Amsterdam Netherlands NL-1054 HB
Citazione:
E.J. 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

Abstract

More than 90% of patients with type III hyperlipoproteinemia are homozygous carriers of the apolipoprotein (apo) E*2 allele. The great majority of these apoE2(Arg158-->Cys) homozygotes in the general population, however, arenormolipidemic. Apparently, expression of the hyperlipidemic state requires additional genetic and/or environmental factors, suggesting a multifactorial etiology. To elucidate these additional risk factors, we analyzed normolipidemic and hyperlipidemic apoE2 homozygotes. Hyperinsulinemia was observed in 27 of 49 apoE2 homozygotes and associated with elevated lipid levels:hyperinsulinemic apoE2 homozygotes had type III hyperlipoproteinemia 6 times more often than apoE2 homozygotes with normal insulin levels (odds ratio6.2, P = 0.02). We screened the normolipidemic and hyperlipidemic apoE2 homozygotes for common variants in candidate genes involved in lipolysis-the APOA1-C3-A4 gene cluster, lipoprotein lipase, and hepatic lipase-and analyzed for associations with the expression of hyperlipidemia. In the hyperinsulinemic group, the 7 carriers of the SstI polymorphism (S2) in the APOC3 gene displayed severely elevated VLDL cholesterol (P-insulin by SstI<0.001) and VLDL triglyceride (P-insulin by SstI<0.01) and low levels of HDL (P-insulin by SstI<0.02) In the normoinsulinemic group, no such relation of the SstI polymorphism with hyperlipidemia was observed. These data provide the first evidence for a combined effect of hyperinsulinemia and the SstI polymorphism on the expression of hyperlipidemia in apoE2 homozygotes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 08:58:58