Variants in STAT5B Associate with Serum TC and LDL-C Levels
2011 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 96, no 9, E1496-E1501 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2011. Vol. 96, no 9, E1496-E1501 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-159237DOI: 10.1210/jc.2011-0322ISI: 000294558600021OAI: oai:DiVA.org:uu-159237DiVA: diva2:443926