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J Clin Endocrinol Metab. 2011 Sep;96(9):E1496-501. doi: 10.1210/jc.2011-0322. Epub 2011 Jul 13.

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

Author information

1
Ludwig Boltzmann Institute for Cancer Research, 1090 Vienna, Austria. jkornfel@uni-koeln.de

Abstract

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.

PMID:
21752895
DOI:
10.1210/jc.2011-0322
[Indexed for MEDLINE]

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