Severe hyperlipidemia in apolipoprotein E2 homozygotes due to a combined effect of hyperinsulinemia and an SstI polymorphism
| Autor: | Eric Sijbrands, Hoffer, M. J. V., Meinders, A. E., Havekes, L. M., Frants, R. R., Smelt, A. H. M., Knijff, P. |
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| Přispěvatelé: | Gaubius instituut TNO |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Apolipoprotein E2 Cholesterol VLDL Gene Expression Hyperlipidemias Polymorphism Single Nucleotide Hyperlipoproteinemia type III Hyperinsulinemia Apolipoproteins E Hyperinsulinism Xanthomatosis Humans Apolipoproteins C Apolipoproteins A Aged Aged 80 and over Family Health Apolipoprotein C-III Apolipoprotein A-I Cholesterol HDL Homozygote nutritional and metabolic diseases Cholesterol LDL Middle Aged Pedigree Haplotypes Xanthomas Female Apolipoprotein E Promoter Regions (Genetics) |
| Zdroj: | CIÊNCIAVITAE Arteriosclerosis, Thrombosis, and Vascular Biology, 11, 19, 2722-2729 Scopus-Elsevier |
| Popis: | 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, are normolipidemic. 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 ratio 6.2, 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) |
| Databáze: | OpenAIRE |
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