title: Variants in STAT5B associate with serum TC and LDL-C levels.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, 1090 Vienna, Austria. jkornfel@uni-koeln.de
authors.forename: Jan-Wilhelm
authors.initials: JW
authors.lastname: Kornfeld
authors.forename: Aaron
authors.initials: A
authors.lastname: Isaacs
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Pospisilik
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
authors.forename: Cornelia
authors.initials: C
authors.lastname: van Duijn
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hicks
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020641:Polymorphism, Single Nucleotide; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D008078:Cholesterol, LDL; D050799:STAT5 Transcription Factor; D002784:Cholesterol