Galanin preproprotein is associated with elevated plasma triglycerides.
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.


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.
Plaisier
Christopher L
CL
Department of Human Genetics, David Geffen School of Medicine at UCLA, Gonda Center, 695 Charles E. Young Drive South, Los Angeles, CA 90095-7088, USA.
Kyttälä
Mira
M
Weissglas-Volkov
Daphna
D
Sinsheimer
Janet S
JS
Huertas-Vazquez
Adriana
A
Riba
Laura
L
Ramírez-Jiménez
Salvador
S
de Bruin
Tjerk W A
TW
Tusié-Luna
Teresa
T
Aouizerat
Bradley E
BE
Pullinger
Clive R
CR
Malloy
Mary J
MJ
Kane
John P
JP
Cruz-Bautista
Ivette
I
Herrera
Miguel F
MF
Aguilar-Salinas
Carlos
C
Kuusisto
Johanna
J
Laakso
Markku
M
Taskinen
Marja-Riitta
MR
van der Kallen
Carla J H
CJ
Pajukanta
Päivi
P
D000273:Adipose Tissue / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology; D005260:Female; D019004:Galanin / Q000097:blood / Q000235:genetics*; D017930:Genes, Reporter; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014162:Transfection; D014280:Triglycerides / Q000097:blood*; D044465:White People
C056567:GAL protein, human; D008055:Lipids; D014280:Triglycerides; D019004:Galanin