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Kornfeld, J.W.* ; Isaacs, A.* ; Vitart, V.* ; Pospisilik, J.A.* ; Meitinger, T. ; Gyllensten, U.* ; Wilson, J.F.* ; Rudan, I.* ; Campbell, H.* ; Penninger, J.M.* ; Sexl, V.* ; Moriggl, R.* ; van Duijn, C.M.* ; Pramstaller, P.P.* ; Hicks, A.A.*

Variants in STAT5B associate with serum TC and LDL-C levels.

J. Clin. Endocrinol. Metab. 96, E1496-E1501 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Context: Known genetic variants influencing serum lipid levels do not adequately account for the observed population variability of these phenotypes. The GH/signal transducers and activators of transcription (STAT) signaling pathway is an evolutionary conserved system that exerts strong effects on metabolism, including that of lipids. Research Design and Methods: We analyzed the association of 11 single-nucleotide polymorphisms (SNP) spanning the STAT5B/STAT5A/STAT3 locus with serum lipid levels in six European populations (n = 5162 nondiabetic individuals). Results: After adjustment for age, sex, alcohol use, smoking, and body mass index, we identified STAT5B variants (rs8082391 and rs8064638) in novel association with total cholesterol (TC; P = 0.001 and P = 0.002) and low-density lipoprotein cholesterol (P = 0.002 and P = 0.004) levels. The minor alleles of these single-nucleotide polymorphisms were significantly enriched in hyperlipidemic individuals across the six discovery populations (P = 0.004 and P = 0.006). In transgenic mice deficient for hepatic STAT5A and STAT5B, reduced serum TC levels coincided with reduced hepatic cholesterol biosynthesis as demonstrated using gene expression profiling and pathway enrichment analysis. Conclusions: Genetic variants in STAT5B are associated with TC and low-density lipoprotein cholesterol levels among six populations. Mechanistically, STAT5B transcriptionally regulates hepatic cholesterol homeostasis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords no keywords
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Journal Journal of Clinical Endocrinology & Metabolism, The
Quellenangaben Volume: 96, Issue: 9, Pages: E1496-E1501 Article Number: , Supplement: ,
Publisher Endocrine Society
Publishing Place Bethesda, Md.
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)