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Variants in STAT5B ...
Variants in STAT5B Associate with Serum TC and LDL-C Levels
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Kornfeld, Jan-Wilhelm (author)
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Isaacs, Aaron (author)
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Vitart, Veronique (author)
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Pospisilik, J. Andrew (author)
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Meitinger, Thomas (author)
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- Gyllensten, Ulf (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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Wilson, James F. (author)
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Rudan, Igor (author)
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Campbell, Harry (author)
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Penninger, Josef M. (author)
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Sexl, Veronika (author)
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Moriggl, Richard (author)
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van Duijn, Cornelia (author)
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Pramstaller, Peter P. (author)
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Hicks, Andrew A. (author)
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(creator_code:org_t)
- The Endocrine Society, 2011
- 2011
- English.
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 96:9, s. E1496-E1501
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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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- By the author/editor
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Kornfeld, Jan-Wi ...
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Isaacs, Aaron
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Vitart, Veroniqu ...
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Pospisilik, J. A ...
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Meitinger, Thoma ...
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Gyllensten, Ulf
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show more...
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Wilson, James F.
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Rudan, Igor
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Campbell, Harry
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Penninger, Josef ...
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Sexl, Veronika
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Moriggl, Richard
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van Duijn, Corne ...
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Pramstaller, Pet ...
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Hicks, Andrew A.
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show less...
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Journal of Clini ...
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Uppsala University