COMMON GENETIC-VARIATION IN THE PROMOTER OF THE HUMAN APO-CIII GENE ABOLISHES REGULATION BY INSULIN AND MAY CONTRIBUTE TO HYPERTRIGLYCERIDEMIA

Citation
Ww. Li et al., COMMON GENETIC-VARIATION IN THE PROMOTER OF THE HUMAN APO-CIII GENE ABOLISHES REGULATION BY INSULIN AND MAY CONTRIBUTE TO HYPERTRIGLYCERIDEMIA, The Journal of clinical investigation, 96(6), 1995, pp. 2601-2605
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
96
Issue
6
Year of publication
1995
Pages
2601 - 2605
Database
ISI
SICI code
0021-9738(1995)96:6<2601:CGITPO>2.0.ZU;2-5
Abstract
Overexpression of plasma apolipoprotein CIII (ape CIII) causes hypertr iglyceridemia in transgenic mice, A genetically variant form of the hu man apo CIII promoter, containing five single base pair changes, has b een shown to be associated with severe hypertriglyceridemia in a patie nt population, In animals and in cultured cells the apo CIII gene is t ranscriptionally downregulated by insulin, In this study we demonstrat e that, unlike the wild-type promoter, the variant promoter was defect ive in its response to insulin treatment, remaining constitutively act ive at all concentrations of insulin, The loss of insulin regulation w as mapped to polymorphic sites at -482 and -455, which fall within a p reviously identified insulin response element, Loss of insulin regulat ion could result in overexpression of the apo CIII gene and contribute to the development of hypertriglyceridemia. The variant apo CIII prom oter is common in the human population and may represent a major contr ibuting factor to the development of hypertriglyceridemia.