Genetic variant of the SREBF-1 gene is significantly related to cholesterol synthesis in man

: Laaksonen R, Thelen KM, Paiva H, Matinheikki J, Vesalainen R, Janatuinen T, Knuuti J, Rontu R, von Bergmann K, Lutjohann D, Lehtimaki T

Publisher: ELSEVIER IRELAND LTD

: 2006

Atherosclerosis

: ATHEROSCLEROSIS

: 185

: 1

: 206

: 209

: 4

: 0021-9150

DOI: https://doi.org/10.1016/j.atherosclerosis.2005.06.007

Sterol regulatory element binding proteins-1 and -2 (SREBPs) are transcription factors controlling lipid homeostasis in human cells. The G-allele carriers of the SREBF-1 gene C-G polymorphism in exon 18c and coding for glycine at the protein level (G952G) have shown to associate more frequently with obesity and type 2 diabetes than the C-allele carriers. However, the C-allele has suggested to be linked to dyslipidemia. Thus, our aim was to study effect of the SREBF-1 gene polymorphism (G952G) on sterol metabolism in man.Ninety-five subjects with moderate hypercholesterolemia participated in this study and 14 homozygous CC carriers of the SREBF-1 (G952G) gene were found. Plasma lathosterol concentration and lathosterol-to-cholesterol ratio, markers of endogenous cholesterol synthesis, were significantly higher in CC homozygous subject compared to others. Similarly muscle cholesterol (p = 0.045) and lathosterol (p = 0.054) concentrations were elevated in the CC homozygotes supporting the view that endogenous cholesterol synthesis rate is SREBF-1 genotype-dependent. (c) 2005 Elsevier Ireland Ltd. All rights reserved.