title: Genetic variant of the SREBF-1 gene is significantly related to cholesterol synthesis in man.
abstract: 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.
authors: Department of Internal Medicine, University Hospital of Tampere, Tampere, Finland. reijo.laaksonen@helsinki.fi
authors: Reijo
authors: R
authors: Laaksonen
authors: Karin M
authors: KM
authors: Thelen
authors: Hannu
authors: H
authors: Päivä
authors: Jussi
authors: J
authors: Matinheikki
authors: Risto
authors: R
authors: Vesalainen
authors: Tuula
authors: T
authors: Janatuinen
authors: Juhani
authors: J
authors: Knuuti
authors: Riikka
authors: R
authors: Rontu
authors: Klaus
authors: K
authors: von Bergmann
authors: Dieter
authors: D
authors: Lütjohann
authors: Terho
authors: T
authors: Lehtimäki
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001706:Biopsy; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D004247:DNA / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D005819:Genetic Markers; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C001521:lathosterol; D004247:DNA; D002784:Cholesterol