Galanin preproprotein is associated with elevated plasma triglycerides

Christopher L. Plaisier, Mira Kyttälä, Daphna Weissglas-Volkov, Janet S. Sinsheimer, Adriana Huertas-Vazquez, Laura Riba, Salvador Ramírez-Jiménez, Tjerk W.A. De Bruin, Teresa Tusié-Luna, Bradley E. Aouizerat, Clive R. Pullinger, Mary J. Malloy, John P. Kane, Ivette Cruz-Bautista, Miguel F. Herrera, Carlos Aguilar-Salinas, Johanna Kuusisto, Markku Laakso, Marja Riitta Taskinen, Carla J.H. Van Der KallenPäivi Pajukanta

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Objective - There is increasing physiological evidence in rodents connecting the neuropeptide galanin to triglyceride (TG) levels. We hypothesized that variation in the galanin preproprotein (GAL) gene may contribute to hypertriglyceridemia (HTG) in humans. Methods and Results - We investigated GAL as a TG candidate gene by genotyping 4 tagSNPs in Dutch, Finnish, and Mexican familial combined hyperlipidemia (FCHL) families as well as in white combined hyperlipidemia cases/controls (n=2471). The common allele of rs2187331, residing in the promoter region of GAL, was significantly associated with HTG (probability value=0.00038). In an unascertained population sample of 4463 Finnish males, the rare allele of rs2187331 was associated with higher TGs (probability value=0.0028 to 0.00016). We also observed an allele specific difference with rs2187331 in reporter gene expression and nuclear factor binding in vitro. Furthermore, we detected differential expression of many key lipid genes in adipose tissue based on rs2187331 genotypes. Conclusions - The SNP rs2187331 is associated with HTG in FCHL and white combined hyperlipidemia cases/controls and influences TG levels in the population. Further studies are warranted to elucidate the allelic difference observed between FCHL and the general population. Functional evidence shows that rs2187331 has an allele specific cis-regulatory function and influences the expression of lipid related genes in adipose.

Original languageEnglish (US)
Pages (from-to)147-152
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number1
DOIs
StatePublished - 2009

Keywords

  • Familial combined hyperlipidemia
  • GAL
  • Genetics of lipid metabolism
  • LPL
  • Triglycerides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Plaisier, C. L., Kyttälä, M., Weissglas-Volkov, D., Sinsheimer, J. S., Huertas-Vazquez, A., Riba, L., Ramírez-Jiménez, S., De Bruin, T. W. A., Tusié-Luna, T., Aouizerat, B. E., Pullinger, C. R., Malloy, M. J., Kane, J. P., Cruz-Bautista, I., Herrera, M. F., Aguilar-Salinas, C., Kuusisto, J., Laakso, M., Taskinen, M. R., ... Pajukanta, P. (2009). Galanin preproprotein is associated with elevated plasma triglycerides. Arteriosclerosis, thrombosis, and vascular biology, 29(1), 147-152. https://doi.org/10.1161/ATVBAHA.108.178533